Compositions and methods for treating inflammasome-related diseases or conditions

Abstract

Biomarkers that can support the diagnosis of inflammatory diseases and methods of their use. [Solution] A composition and method for detecting inflammasome components in a sample from a subject as a marker for inflammasome-related diseases or disorders such as multiple sclerosis, stroke, mild cognitive impairment, Alzheimer's disease, age-related macular degeneration, NASH, inflammatory aging, or traumatic brain injury. Methods for using such inflammasome markers to determine prognosis, prescribe treatment, and monitor response to treatment in subjects with inflammasome-related diseases or disorders such as multiple sclerosis, stroke, mild cognitive impairment, Alzheimer's disease, age-related macular degeneration, NASH, inflammatory aging, or traumatic brain injury are also described.

Description

[Technical Field]

[0001] Cross-reference of related applications This application relates to the specification of U.S. Provisional Patent Application No. 63 / 062,622, filed on August 7, 2020. and the specification of U.S. Provisional Patent Application No. 63 / 016,033 filed on April 27, 2020 (each These documents (which are incorporated herein by reference in their entirety for all purposes) have priority over the respective documents. I assert.

[0002] Description of research funded by the federal government. This invention was developed by the National Institute of Neurological Disorders and Stroke. f Neurological Disorders and Stroke)(NIN Grant number 4R42NS086274-02 awarded by DS and the National Institutes of Health Grant awarded by the National Institute of Health This was done with the support of the U.S. government under financial code 5R42NS086274-03. The government has certain rights relating to this invention.

[0003] This invention generally relates to the fields of immunology and medicine. More specifically, this invention relates to ASC (Apoptosis-related specs containing caspase-activating recruitment domains (CARDs)) Protein activity, caspase-1, IL-18, IL-1β, NOD-like receptor (NLR) ), absent-in-melanoma 2 (AIM2)-like receptor (ALR) and other inflammas The globulin protein alone, or in multiple sclerosis (MS), stroke, and mild cognitive impairment (MCI) Alzheimer's disease (AD), age-related macular degeneration (AMD), age-related inflammation or traumatic brain injury Biomarkers for diseases, conditions, or disorders such as traumatic brain injury (TBI) from mammals Detection is performed by combining the obtained sample with the control biomarker protein. The present invention relates to compositions and methods for the following: Finally, the present invention provides a simple solution for neurological diseases, disorders and / or pathological conditions. In Germany, or using an agent targeting the inflammasome protein, the inflammasome This paper describes a treatment method that combines assessment of masome protein expression levels.

[0004] Description of sequence listings The sequence listings related to this application are provided in text format instead of paper copies and are for reference only. This will be incorporated more into this specification. The name of the text file containing the sequence listing is UNMI_01 The file is 5_03WO_SeqList_ST25.txt. The text file contains approximately 43 entries. This is a KB article, created on April 27, 2021, and submitted electronically via EFS-Web. It is. [Background technology]

[0005] Multiple sclerosis (MS) is a progressive autoimmune disorder that affects the central nervous system (CNS). Pathologically, it is caused by demyelination and the presence of inflammatory lesions in the spinal cord and brain. Characterized by (Compston A. The pathogenesis and basis for treatment in multiple sclerosis is.Clin Neurol Neurosurg.2004;106:246-8) Clinically, MS patients experience blurred vision, muscle weakness, fatigue, dizziness, and balance and gate problems. (Compston A. The pathogenesis and basis) s for treatment in multiple sclerosis.Cl (in Neurol Neurosurg. 2004;106:246-8). United States only. There are 400,000 MS patients in Japan, and approximately 2 million patients worldwide (Compst on A.The pathogenesis and basis for trea tment in multiple sclerosis.Clin Neurol Neurosurg. 2004;106:246-8).

[0006] Since the 1960s, immunoglobulin (Ig) G oligoclonal bands (OCBs) , has been used as a classic biomarker for diagnosing MS (Stangel M, Fr Edrikson S, Meinl E, Petzold A, Stuve O and Tumani H.The utility of cerebrospinal f luid analysis in patients with multiple sclerosis.Nat Rev Neurol.2013;9:267-76). However, the specificity of IgG-OCB is only 61%, and as a result, diagnosing MS is difficult. Other diagnostic criteria are needed for clinical determination (Teunissen CE, M alekzadeh A, Leurs C, Bridel C and Killest ein J.Body fluid biomarkers for multiple sclerosis--the long road to clinical ap plication.Nat Rev Neurol.2015;11:585-96) Nevertheless, CSF-restricted IgG-OCB can be detected independently of MRI, from CIS to CDM. It is a good predictor of transition to S (Tintore M, Rovira A, Rio J, Tur C, Pelayo R, Nos C, Tellez N, Perkal H ,Comabella M,Sastre-Garriga J and Montal ban X.Do oligoclonal bands add informati on to MRI in first attacks of multiple s clerosis? Neurology. 2008;70:1079-83). Similar The results were obtained when analyzing IgM-OCB (Villar LM, Masj). uan J, Gonzalez-Porque P, Plaza J, Sadaba M C, Roldan E, Bootello A and Alvarez-Cermen o JC.Intrathecal IgM synthesis predictions the onset of new relapses and a worse di sease course in MS.Neurology.2002;59:555 -9). An important research area in the field of MS is predicting who is at risk of developing MS. Suitable biomarkers, biomarkers for disease progression or exacerbation, and biomarkers for treatment response and prognosis This involves identifying iomarkers.

[0007] There are 17.5 million deaths related to cardiovascular disease each year, of which 6.7 million are due to... , which occurs as a result of stroke (Mendis S, Davis S and Norr ving B.Organizational update:the world h wealth organization global status report on noncommunicable diseases 2014;one mor e landmark step in the combat against st roke and vascular disease.Stroke.2015;46 :e121-2). Several large-scale trials have been conducted on biomarkers for stroke. However, the gold standard biomarker used in the care of stroke patients is still There is no such thing. There is a need for a biomarker that exhibits high sensitivity and high specificity for stroke. It still exists.

[0008] U.S. Centers for Disease Control and Prevention l) The CDC defines traumatic brain injury (TBI) as "a collision, blow or impact to the head or a puncture to the head." It is defined as "the disruption of normal brain function that may result from a common head injury." 201 As of 2000, the CDC reported 823.7 TBI-related emergency cases per 100,000 individuals in the United States. In-home examinations, hospitalizations, and deaths were recorded. (Centers for Disease Control and Prevention's "Traumatic Brain Injury and Concussion") Website: www.cdc.gov / traumaticbraininjury / index.html (as of June 21, 2018). Important research areas in the field of TBI. This includes suitable biomarkers for TBI risk, disease diagnosis, and biomarkers for progression or exacerbation. - Furthermore, the identification of biomarkers for treatment response and prognosis. Inflammasome proteins It has been shown that inflammasomes can be used as a biomarker after traumatic brain injury. This was suggested by previous research. The inflammasome is involved in the activation of caspase-1 and flame Innate immune responses involved in the processing of symptomatic cytokines IL-1 beta and IL-18. It is a multi-protein complex responsible for [something]. The inflammasome is particularly important after brain and spinal cord injury. It contributes to the inflammatory response.

[0009] During aging, chronic aseptic low-grade inflammation (known as inflammatory aging) develops, leading to age-related diseases. It contributes to the development of pathology. From an evolutionary perspective, it involves pathogens (non-self), endogenous cell debris, and misdistribution. Various stimuli, including molecules (self), nutrients, and the gastrointestinal microbiome (semi-self), This sustains inflammatory aging. Degeneracy leads to recognition of more signals and activation of innate immune responses. A limited number of receptors that enable this process sense these stimuli. However, inflammation Biomarkers that can support the diagnosis of aging and for the treatment of inflammatory aging and / or age-related diseases. There is a lack of available therapeutic targets and / or therapeutic agents. [Overview of the Initiative] [Problems that the invention aims to solve]

[0010] A borderline or transitional state between normal aging and dementia, or a theme of Alzheimer's disease (AD) Much interest has been shown regarding this condition. Regarding this pathological condition, mild cognitive impairment (MCI) has been discussed. Several descriptions have been made regarding this condition, including first-onset dementia and isolated memory impairment. The criteria for mild cognitive impairment (MCI) include memory impairment that exceeds expectations for age and educational attainment in the absence of dementia. These can be harmful. These targets are becoming the focus of many predictive and early intervention trials. Yes, it exists. However, the diagnostic criteria for MCI are not generally clearly defined, and bio The presence of markers is lacking. Furthermore, it is in an early stage compared to more advanced stages of AD. Diagnosing the appropriate stage is essential for improving treatment outcomes.

[0011] Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and in the United States 11 million people in Japan and over 170 million people worldwide have been affected. AMD, It is a progressive degenerative disease that can cause irreversible vision loss. Patients with this condition often experience no symptoms, and the disease typically begins with the onset of vision loss. It is not detected until later in the disease. Currently, AMD is incurable, therefore it is in the early stages of AMD. To diagnose and slow its progression, observable data to promote disease screening are available. Identifying the iomarker is absolutely essential. (Zarbin MA.Current) concepts in the pathogenesis of age-rel ated macular degeneration.Arch Ophthalmo l 2004;122:598-614., Ozaki E, Campbell M,K iang AS, Humphries M, Doyle SL, Humphries P .Inflammation in age-related macular deg. eneration.Adv Exp Med Biol 2014;801:229- 235. [Means for solving the problem]

[0012] Therefore, to address the needs identified above, what is presented herein is inflammation Ingredients are useful as biomarkers with high sensitivity and specificity for various pathological conditions. The pathological condition is treated by targeting the flammasome components and the said flammasome components. This is the method.

[0013] In one embodiment, this specification describes how to evaluate patients suspected of having multiple sclerosis (MS). A method is provided, which involves at least one type of ion in a biological sample obtained from a patient. Measuring the levels of phrasome proteins and protein signatures related to MS The purpose is to determine the presence or absence of a protein signature, and the protein signature is elevated. It is determined that the patient has at least one inflammasome protein, and that the patient has If a protein signature is present, the patient should be selected as having MS. Includes. In some cases, patients present with clinical symptoms consistent with MS. MS includes relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS. It is either PPMS (periadal recurrent MS) or progressive recurrent MS (PRMS). In some cases, it is obtained from the patient. The biological samples included cerebrospinal fluid (CSF), CNS microdialysis fluid, saliva, serum, plasma, and urine. Alternatively, they are extracellular vesicles (EVs) derived from serum. In some cases, they are found in the protein signature. The level of at least one inflammasome protein is present in the protein signature. This method utilizes one or more antibodies targeted at at least one type of inflammasome protein. It is measured by an immunoassay. In some cases, at least one type of inflamma Somal proteins include interleukin-18 (IL-18), IL-1 beta, and casper proteins. Apoptosis-related speck-like proteins (ASCs) containing a ze-mobilization domain, caspar It is either Ze-1 or a combination thereof. In some cases, it is at least one type of inflammasome. The proteins include caspase-1, IL-18, IL-1 beta, and ASC. In some cases, at least one type of inflammasome protein contains ASCs. In this case, the antibody has a PYRIN-PAAD-DAPIN domain (PYD), and a C-terminal Spase mobilization domain (CARD) domain or PYD or CA of ASC protein It binds to a portion of the RD domain. In some cases, it binds to a small portion of the protein signature. The levels of one type of inflammasome protein were obtained from the biological control. Enhanced levels of at least one inflammasome protein in the sample In some cases, biological samples obtained from controls are cerebrospinal fluid (CS). F) CNS microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EVs). In some cases, the control group consists of healthy individuals, and these healthy individuals exhibit clinical symptoms consistent with MS. This is an individual that does not exhibit symptoms. In some cases, at least one species of inflammasometa The protein contains ASC, and the ASC level is obtained from the biological sample of the control. It is at least about 50% higher than the ASC level during the pull. In some cases, protein levels The level of at least one inflammasome protein in the texture is a predetermined reference value. Or it is augmented relative to the range of reference values. In some cases, biological data obtained from patients The sample is serum, and the patient is at least about 80%, about 85%, about 90%, about 9% Having MS with sensitivity of 5%, approximately 99%, or approximately 100% and specificity of at least approximately 90% They are selected. In some cases, the biological sample is serum, and the patient is small. At least with a specificity of approximately 80%, 85%, 90%, 95%, 99%, or 100% M It is selected as having S. In some cases, the biological sample is serum, and Patients are selected as having MS with at least 90% sensitivity and at least 80% specificity. Selected. In some cases, at least one inflammasome protein is selected for the ASC. Includes. In some cases, the cutoff values ​​for determining sensitivity, specificity, or both are shown in the table. Selected from 7. In some cases, the sensitivity and / or sensitivity are received with a 95% confidence interval. It is determined using the area under the curve (AUC) from the operating characteristic curve (ROC).

[0014] In another aspect, this specification provides a method for evaluating a patient suspected of having suffered a stroke. This method provides a biological sample obtained from a patient containing at least one type of insect. Measuring ramasomal protein levels and their relationship to stroke or stroke-related injury To determine the presence or absence of a protein signature, - This determines that the elevated levels include at least one type of inflammasome protein. Furthermore, if a patient exhibits the presence of a protein signature, it is considered that they have suffered a stroke. This includes selecting patients. In some cases, patients have clinical symptoms consistent with stroke. The symptoms include ischemic stroke, transient ischemic stroke, or hemorrhagic stroke. In some cases, the biological samples obtained from the patient were cerebrospinal fluid (CSF), CNS microparticles. Dialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EVs). In some cases... The level of at least one inflammasome protein in the protein signature is , directed toward at least one inflammasome protein in the protein signature It is measured by an immunoassay using one or more antibodies. At least one inflammasome protein is interleukin-18 (IL-18) ), IL-1 beta, apoptosis-related specular type containing caspase mobilization domain It is protein (ASC), caspase-1, or a combination thereof. In some cases, less At least one type of inflammasome protein is involved in caspase-1, IL-18, and IL-1 β. Includes each of the following: and ASC. In some cases, at least one inflammasome tan. The protein contains ASC. In some cases, the antibody is PYRIN-PAAD-DAPIN Domain (PYD), C-terminal caspase mobilization domain (CARD) domain, or ASC domain It binds to a portion of the PYD or CARD domain of protein. In some cases, The level of at least one inflammasome protein in the protein signature is At least one inflammasome protein in biological samples obtained from trolls It is enhanced in terms of quality level. In some cases, the biological results obtained from the control are enhanced. Suitable samples include cerebrospinal fluid (CSF), CNS microdialysis fluid, saliva, serum, plasma, urine, or serum. These are derived extracellular vesicles (EVs). In some cases, the control is a healthy individual, and A normal individual is one that does not exhibit clinical symptoms consistent with MS. In some cases, less Both inflammasome proteins contain ASCs, and serum samples obtained from the subjects... The ASC level in the sample is different from the ASC level in the serum sample obtained from the control. It is at least 70% higher. In some cases, at least one type of inflammasome protein The substance contains ASC, and the level of ASC in the serum-derived EV sample obtained from the subject was, The level of ASC in serum-derived EV samples obtained from the control is at least 1 10% higher. In some cases, at least one type of inflamma in the protein signature. Somal protein levels are enhanced against a predetermined reference value or range. In some cases, the biological sample obtained from the patient is serum, and the patient is small. Sensitivity of at least 80%, 85%, 90%, 95%, 99%, or 100% Even without a diagnosis, it is selected with approximately 90% specificity as a stroke patient. In some cases, The biological sample is serum, and the patient is at least about 80%, about 85%, about 90% Selected with a specificity of %, approximately 95%, approximately 99%, or approximately 100% as having suffered a stroke. In some cases, the biological sample is serum, and the patient is at least 100 It is selected as having suffered a stroke with a certain percentage of sensitivity and at least 95% specificity. In some cases, at least one inflammasome protein contains an ASC. In this case, the cutoff value for determining sensitivity, specificity, or both is selected from Table 8. In some cases, the biological samples obtained from patients are serum-derived EVs, and Patients have at least approximately 80%, 85%, 90%, 95%, 99%, or 100% It is selected as having suffered a stroke with a sensitivity and specificity of at least approximately 90%. In this case, the biological sample is serum-derived EV, and the patient is at least about 80 The probability of suffering a stroke is approximately 85%, 90%, 95%, 99%, or 100%. It is selected as such. In some cases, the biological sample is serum-derived EV, And the patient suffered a stroke with at least 100% sensitivity and at least 100% specificity. It is selected as having done so. In some cases, at least one type of inflammasome protein The substance includes ASC. In some cases, the substance is used to determine sensitivity, specificity, or both. The set-off value is selected from Table 9. In some cases, the sensitivity and / or sensitivity is 95%. The confidence interval is determined using the area under the curve (AUC) from the receiver operating characteristic (ROC) curve. ru.

[0015] In yet another embodiment, this specification describes how to treat patients diagnosed with multiple sclerosis (MS). A method is provided which includes administering standard treatment procedures for MS to the patient, and the diagnosis of MS The diagnosis was elevated levels of at least one type of influenza in biological samples obtained from patients. This is done by detecting lamasomal proteins. In some cases, MS is relapsing and relapsing. Resolving MS (RRMS), Secondary Progressive MS (SPMS), Primary Progressive MS (PPMS) or This is progressive recurrent MS (PRMS). In some cases, standard treatment measures modify the disease outcome. Therapies are selected from those aimed at managing relapses, managing symptoms, or a combination thereof. In some cases, therapeutic agents aimed at modifying disease outcomes include β-interferon, vinegar, etc. Acid glatiramer, fingolimod, teriflunomide, dimethyl fumarate, mitoxant Selected from lon, ocrelizumab, alemtuzumab, daclizumab, and natalizumab. .

[0016] In yet another aspect, this specification includes a patient diagnosed with a stroke or stroke-related injury. A method of treatment is provided, which allows patients to receive standard treatment for stroke or stroke-related injury. The diagnosis of stroke or stroke-related injury, including administering a biological sample obtained from the patient, is based on the following: The goal is to detect elevated levels of at least one type of inflammasome protein in the sample. It is performed more often. In some cases, a stroke is an ischemic stroke, a transient ischemic stroke, or a hemorrhagic stroke. It is an ischemic stroke. In some cases, the stroke is either an ischemic stroke or a transient ischemic stroke. Standard treatment involves tissue plasminogen activator (tPA), antiplatelet drugs, Anticoagulants, carotid angioplasty, carotid endarterectomy, intra-arterial thrombolysis, and mechanical blood clot removal during cerebral ischemia. It is selected from (MERCI) or a combination thereof. In some cases, stroke This is a hemorrhagic stroke, and the standard treatment is aneurysm clipping, coil embolization, or This is venous malformation (AVM) repair. In some cases, at least one type of elevated level Inflammasome proteins are directed toward at least one type of inflammasome protein. It is measured by an immunoassay using one or more antibodies. The level of at least one inflammasome protein was higher in the control sample. It is enhanced to the level of at least one inflammasome protein. In that case, the level of at least one inflammasome protein is equal to a predetermined reference value or It is augmented with respect to the range of the reference value. In some cases, at least one type of infrastructure The chromium protein contains interleukin-18 (IL-18) and a caspase recruitment domain. apoptosis-related speck-like proteins (ASCs), caspases-1 or their It is a combination. In some cases, at least one inflammasome protein is a combustible component. These are Pase-1, IL-18, and ASC. In some cases, at least one type of infrastructure The masome protein is ASC. In some cases, the antibody is PYRIN-PAAD. - DAPIN domain (PYD), C-terminal caspase mobilization domain (CARD) domain Alternatively, it binds to a portion of the PYD or CARD domain of the ASC protein. In this case, the biological samples are cerebrospinal fluid (CSF), CNS microdialysis fluid, saliva, serum, and blood. These are extracellular vesicles (EVs) derived from plasma, urine, or serum.

[0017] In further embodiments, this specification may include patients suspected of having traumatic brain injury (TBI). A method for evaluating individuals is provided, and this method is used to evaluate the small amount of biological samples obtained from patients. Both involve measuring the level of one type of inflammasome protein and TBI-related factors. To determine the presence or absence of a protein signature, This involves determining that the elevated levels include at least one type of inflammasome protein. Furthermore, if a patient presents with a protein signature, the patient is considered to have TBI. This includes making a selection. In some cases, the patient presents with clinical symptoms consistent with TBI. In some cases, the biological samples obtained from the patient are cerebrospinal fluid (CSF), CN These are microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EVs). In this case, the protein signature contains at least one inflammasome protein. Bell identified at least one inflammasome protein in the protein signature. It is measured by an immunoassay that uses one or more antibodies directed at it. In this case, at least one inflammasome protein is interleukin-18 (IL -18) Apoptosis-related specs containing IL-1β and caspase recruitment domains It is a protein (ASC), caspase-1, or a combination thereof. In some cases, small At least one type of inflammasome protein contains caspase-1. In some cases... At least one inflammasome protein contains an ASC. In some cases, anti The body has a PYRIN-PAAD-DAPIN domain (PYD), and a C-terminal caspase mobilization domain. The main (CARD) domain or the PYD or CARD domain of the ASC protein It binds to a portion. In some cases, at least one ingredient in the protein signature. Flamasomal protein levels were low in biological samples obtained from the control. At least one type of inflammasome protein is enhanced. In this case, at least one inflammasome protein contains caspase-1, and The level of caspase-1 is measured in the biological sample obtained from the control. It is at least about 50% higher than the level. In some cases, at least one type of infrastructure Somal proteins include ASCs, and the level of ASCs is obtained from organisms compared to controls. At least 50% higher than the ASC level in the academic sample. In some cases, control The biological samples obtained from the rolls were cerebrospinal fluid (CSF), CNS microdialysis fluid, and saliva. These are serum, plasma, urine, or serum-derived extracellular vesicles (EVs). In some cases, control A healthy individual is one that does not exhibit clinical symptoms consistent with TBI. In some cases, at least one inflammasome protein is present in the protein signature. The protein level is enhanced against a given reference value or range of reference values. In this case, the biological sample obtained from the patient is serum, and the patient is at least approximately Sensitivity of 80%, approximately 85%, approximately 90%, approximately 95%, approximately 99%, or approximately 100% and at least It is selected as having TBI with a specificity of approximately 90%. In some cases, biological samples The substance is serum, and the patient is at least about 80%, about 85%, about 90%, and about 95%. It is selected as having TBI with a specificity of approximately 99% or approximately 100%. In some cases, The biological sample is serum, and the patient has at least 90% sensitivity and at least It is selected as having TBI with 80% specificity. In some cases, sensitivity and / or sensitivity The degree is calculated by taking the area under the curve (AUC) from the receiver operating characteristic (ROC) curve with a 95% confidence interval. Determined using. In some cases, at least one inflammasome protein is Includes ASC. In some cases, cutoffs for determining sensitivity, specificity, or both. The value is selected from Tables 11B, 12B, 14A, 16, 17, or 19. In some cases... At least one inflammasome protein contains caspase-1. In this case, the cutoff value for determining sensitivity, specificity, or both is shown in Table 11A or 15. It will be selected.

[0018] In yet another embodiment, this specification provides a method for evaluating a patient suspected of having brain injury. This method provides a biological sample obtained from a patient containing at least one type of insect. Measuring the levels of ramasomal proteins and protein signatures associated with brain damage The purpose is to determine the presence or absence of the protein signature, and the protein signature is elevated at the level. It is determined that the patient has at least one inflammasome protein. When a protein signature is present, the patient should be selected as having brain damage. In some cases, patients present with clinical symptoms consistent with brain injury. In total, the biological samples obtained from patients were cerebrospinal fluid (CSF), CNS microdialysis fluid, and saliva. These are fluids, serum, plasma, urine, or serum-derived extracellular vesicles (EVs). In some cases, proteins The level of at least one inflammasome protein in the quality signature is protein A signal directed at at least one inflammasome protein in the quality signature. It is measured by immunoassays using more than 10 types of antibodies. In some cases, at least Another type of inflammasome protein is interleukin-18 (IL-18), IL- 1β, an apoptosis-related speck-like protein containing a caspase recruitment domain (AS C) Caspase-1 or a combination thereof. In some cases, at least one type The phrasome protein contains ASC. In some cases, the antibody is PYRIN-P AAD-DAPIN domain (PYD), C-terminal caspase mobilization domain (CARD) It binds to a portion of the PYD or CARD domain of the main or ASC protein. In some cases, at least one inflammasome protein contains caspase-1. In some cases, at least one inflammasome protein is present in the protein signature. Protein levels are determined by the presence of at least one type of protein in the biological sample obtained from the control. It is enhanced against the levels of phrasome proteins. In some cases, at least Another type of inflammasome protein contains ASC, and the level of ASC is controlled The levels of ASC in biological samples obtained from the source are at least 50% higher. In some cases, at least one inflammasome protein contains caspase-1, The level of caspase-1 is compared to the level of caspase-1 in biological samples obtained from the control. -50% higher than the -1 level. In some cases, obtained from the control. The biological samples included cerebrospinal fluid (CSF), CNS microdialysis fluid, saliva, serum, plasma, and urine. Alternatively, they are serum-derived extracellular vesicles (EVs). In some cases, controls are healthy individuals. In some cases, healthy individuals are those that do not exhibit clinical symptoms consistent with brain damage. In addition, brain injury is selected from traumatic brain injury, stroke, mild cognitive impairment, or multiple sclerosis. In some cases, at least one inflammasome protein in the protein signature The quality level is enhanced against a predetermined reference value or range of reference values. In general, brain injury is traumatic brain injury (TBI). In some cases, biological samples obtained from the patient are used. The medical sample is serum, and the patient is at least about 80%, about 85%, about 90%. TBI is detected with approximately 95%, 99%, or 100% sensitivity and at least approximately 90% specificity. It is selected as such. In some cases, the biological sample is serum, and the patient , at least about 80%, about 85%, about 90%, about 95%, about 99%, or about 100% specific It is selected as having TBI at a certain degree. In some cases, the biological sample is serum. Furthermore, the patient has TBI with at least 90% sensitivity and at least 80% specificity. Selected as such. In some cases, sensitivity and / or reception are received within a 95% confidence interval. It is determined using the area under the curve (AUC) from the ROC curve. In some cases, at least one inflammasome protein contains ASC. The cutoff values ​​for determining sensitivity, specificity, or both are shown in Tables 11B, 12B, and 14. Selected from A, 16, 17, or 19. In some cases, at least one type of infrastructure. Somal proteins include caspase-1. In some cases, sensitivity, specificity, or both. The cutoff value for determining the method is selected from Table 11A or 15. In some cases... Brain damage results in mild cognitive impairment (MCI). In some cases, biological findings obtained from patients... The sample is serum, and the patient is at least 75%, 80%, 85%, 90%. Selected as having MCI with a sensitivity of 95%, 99%, or 100%. In some cases The biological sample is serum, and the patient is at least about 55%, about 60%, about 6% 5%, approximately 70%, approximately 75%, approximately 80%, approximately 85%, approximately 90%, approximately 95%, approximately 99%, or approximately Selected as having MCI with 100% specificity. In some cases, biological samples The substance is serum, and the patient has at least 90% sensitivity and at least 70% specificity. Selected as having MCI. In some cases, sensitivity and / or sensitivity is 95% The confidence interval is determined using the area under the curve (AUC) from the receiver operating characteristic (ROC) curve. In some cases, at least one inflammasome protein contains an ASC. In some cases, the cutoff values ​​for determining sensitivity, specificity, or both are shown in Table 22 or It is selected from 23. In some cases, at least one inflammasome protein. This includes IL-18. In some cases, to determine sensitivity, specificity, or both, The set-off value is selected from Table 22 or 25. In some cases, brain injury is multiple sclerosis. It is MS. In some cases, the biological sample obtained from the patient is serum. , and patients are at least about 80%, about 85%, about 90%, about 95%, about 99%, or about 1 It is selected as having MS with 00% sensitivity and at least about 90% specificity. In that case, the biological sample is serum, and the patient is at least about 80%, about 85% Selected as having MS with specificity of %, approximately 90%, approximately 95%, approximately 99%, or approximately 100%. In some cases, the biological sample is serum, and the patient is at least 90 Selected as having MS with % sensitivity and at least 80% specificity. In some cases, at least one inflammasome protein contains an ASC. The cutoff values ​​for determining sensitivity, specificity, or both are selected from Table 7. In the case of a receiver, sensitivity and / or responsiveness are measured in the receiver operating characteristic (ROC) curve with a 95% confidence interval. It is determined using the area under the curve (AUC). In some cases, brain injury is due to stroke. Yes. In some cases, the biological sample obtained from the patient is serum, and the patient , with a sensitivity of at least approximately 80%, 85%, 90%, 95%, 99%, or 100% And they are selected as having had a stroke with a specificity of at least 90%. In combination, the biological sample is serum, and the patient is at least about 80%, about 85%, about Selected with a specificity of 90%, approximately 95%, approximately 99%, or approximately 100% that the individual has had a stroke. In some cases, the biological sample is serum, and the patient is at least 1 Individuals are selected as having suffered a stroke with 00% sensitivity and at least 95% specificity. In some cases, at least one type of inflammasome protein contains ASCs. In this case, the cutoff value for determining sensitivity, specificity, or both is selected from Table 8. In some cases, the biological samples obtained from the patient are serum-derived extracellular viable cells (EVs). And patients are at least about 80%, about 85%, about 90%, about 95%, about 99%, or about 10% It is selected as having suffered a stroke with 0% sensitivity and at least 90% specificity. In some cases, the biological sample is serum-derived EV, and the patient is at least about 8 Stroke occurs with specificity of 0%, approximately 85%, approximately 90%, approximately 95%, approximately 99%, or approximately 100%. It is selected as such. In some cases, the biological sample is serum-derived EV. , and the patient suffered a stroke with at least 100% sensitivity and at least 100% specificity. Selected as having the disease. In some cases, at least one type of inflammasome tan. The protein contains ASC. In some cases, to determine sensitivity, specificity, or both. The cutoff value is selected from Table 9. In some cases, the sensitivity and / or sensitivity is 95%. The confidence interval is determined using the area under the curve (AUC) from the receiver operating characteristic (ROC) curve. It can be done.

[0019] In further embodiments, this specification may include information regarding patients suspected of having mild cognitive impairment (MCI). A method for evaluating individuals is provided, and this method is used to evaluate the small amount of biological samples obtained from patients. Both involve measuring the level of one type of inflammasome protein and MCI-related factors. To determine the presence or absence of a protein signature, This involves determining that the elevated levels include at least one type of inflammasome protein. Furthermore, if a patient presents with a protein signature, the patient is considered to have MCI. This includes making a choice. In some cases, the patient presents with clinical symptoms consistent with MCI. In some cases, the biological samples obtained from the patient are cerebrospinal fluid (CSF), CN These are microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EVs). In this case, the protein signature contains at least one inflammasome protein. Bell identified at least one inflammasome protein in the protein signature. It is measured by an immunoassay that uses one or more antibodies directed at it. In this case, at least one inflammasome protein is interleukin-18 (IL -18) Apoptosis-related specs containing IL-1β and caspase recruitment domains It is a protein (ASC), caspase-1, or a combination thereof. In some cases, small At least one type of inflammasome protein contains ASC. In some cases, less Both inflammasome proteins contain IL-18. In some cases, antibodies PYRIN-PAAD-DAPIN domain (PYD), C-terminal caspase mobilization domain The CARD domain or part of the PYD or CARD domain of the ASC protein It binds to the protein signature. In some cases, at least one type of infrastructure in the protein signature. The levels of masome protein were lower in biological samples obtained from the control. Both are enhanced to the level of one type of inflammasome protein. In total, at least one inflammasome protein contains ASC, and the level of ASC is at least 50% higher than the ASC level in the biological samples obtained from the control. % higher. In some cases, at least one inflammasome protein is IL-18 The level of IL-18, including the IL-18 level in the biological samples obtained from the control, was It's at least about 25% higher than level 18.

[0020] In one embodiment, this specification describes how to evaluate patients suspected of having mild cognitive impairment (MCI). A method is provided which involves at least one type of biological sample obtained from a patient. Measuring the expression levels of inflammasome proteins and the small amount in biological samples At least one inflammasome protein expression level is controlled by one or more control MCIs. Comparing with the expression levels of biomarkers and at least one of the biological samples Control MCI biomarkers with expression levels of one or more inflammasome proteins This includes selecting patients as having MCI if their expression levels are similar to those of the other condition. In some cases, the expression level or expression of at least one inflammasome protein. The parameter representing the level is the expression level of one or more control MCI biomarkers. 10%, 9%, 8%, 7%, 6%, 5%, 4% of the parameter representing the expression level. If the percentage is within 3%, 2%, or 1%, then at least one type of inflammasome protein is produced. The current level is similar to the expression level of one or more control MCI biomarkers. In some cases, the expression levels of one or more control MCI biomarkers are higher in patients. It is measured in biological samples obtained from. In some cases, one or more controls The expression levels of the MCI biomarker were obtained from individuals previously diagnosed with MCI. It is measured in physical samples. In some cases, it is obtained from individuals previously diagnosed with MCI. The biological samples obtained were the same as those obtained from patients suspected of having MCI. It is a type of biological sample. In some cases, it is at least one type of inflammasome. Protein expression levels and expression levels of one or more control MCI biomarkers This refers to at least one type of inflammasome in biological samples obtained from controls. Protein expression levels and expression levels of one or more control MCI biomarkers It is enhanced against. In some cases, biological samples obtained from controls This is the same type of biological sample obtained from patients suspected of having MCI. In some cases, the control group consists of healthy individuals, and these healthy individuals are MCI. These are individuals that do not exhibit the clinical symptoms that cause the disease. In some cases, at least one type of infrastructure The expression level of masome proteins and the expression of one or more control MCI biomarkers. The current level includes at least one inflammasome protein and one or more control proteins. Enhanced relative to a specified reference value or range for MCI biomarkers. In some cases, the expression level of at least one inflammasome protein is represented by Parameters representing the expression levels of the meter and one or more control MCI biomarkers The metric is the area under the curve (AUC). In some cases, patients have clinical symptoms consistent with MCI. The patient is exhibiting bedridden symptoms. In some cases, it is obtained from patients suspected of having MCI. The biological samples included cerebrospinal fluid (CSF), CNS microdialysis fluid, saliva, serum, plasma, and urine. Or it is a serum-derived extracellular vesicle (EV). In some cases, at least one type of inflamma Expression levels of somal proteins and / or one or more control MCI biomarkers This includes at least one inflammasome protein and / or one or more control M By an immunoassay using one or more antibodies directed against a CI biomarker It is measured by... In some cases, at least one inflammasome protein is in Apo containing tarleukin 18 (IL-18), IL-1β, and caspase mobilization domain Tosis-related speck-like protein (ASC), caspase-1, or a combination thereof In some cases, at least one inflammasome protein contains an ASC. In some cases, at least one inflammasome protein contains IL-18. In some cases, one or more control MCI biomarkers are neurofilament Trilite polypeptide (NFL), soluble APP-alpha (sAPPα) and / or soluble It is soluble APP-beta (sAPPβ). In some cases, it is at least one type of infrastructure. The masome protein is an ASC, and one or more control MCI biomarkers - is soluble APP-alpha (sAPPα), and the AUC of ASC is 0.974. Yes, and the AUC of sAPP-alpha is 0.9687. In some cases, less At least one type of inflammasome protein is an ASC, and one or more controllers The MCI biomarker is soluble APP-beta (sAPPβ), and is the AU of ASC. C is 0.974, and the AUC of sAPP-beta is 0.9068. In the case of Tsuka, at least one inflammasome protein is ASC, and one The above control MCI biomarkers are neurofilament light polypeptides. (NFL) The AUC of ASC is 0.974, and the AUC of NFL is 0. It is 7734. In some cases, the biological sample obtained from the patient is serum. And patients are at least 70%, 75%, 80%, 85%, 90%, 95%, 99% or It is selected as having MCI with 100% sensitivity and at least 55% specificity. In this case, the biological sample obtained from the patient is serum, and the patient is at least Also with MC sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is selected as having I. In some cases, the biological sample obtained from the patient is The serum, and the patient, showed MC with at least 70% sensitivity and at least 55% specificity. It is selected as having I. In some cases, the specificity and / or sensitivity are 95% confident. The interval is determined using a receiver operating characteristic (ROC) curve. In some cases, the method is determined using a receiver operating characteristic (ROC) curve. To select a patient as having MCI, the presence of one or more symptoms associated with MCI. Further includes evaluating the following: In some cases, one or more symptoms associated with MCI are present in healthy individuals. Forgetfulness, lack of concentration, anxiety, difficulty making decisions, difficulty understanding instructions, difficulty planning, difficulty moving in unfamiliar environments. The time required to make an impulsive or suspicious judgment and to complete a complex task or visual perception. This is a judgment regarding order.

[0021] In another embodiment, this specification includes a patient suspected of having Alzheimer's disease (AD). A method for evaluation is provided, and this method is used to evaluate at least one of the biological samples obtained from the patient. Measuring the expression level of one type of inflammasome protein and in biological samples The expression level of at least one inflammasome protein is controlled by one or more factors. To compare with the expression levels of AD biomarkers, and at least one in the biological sample Control AD ​​biomers with expression levels of one or more species of inflammasome proteins This includes selecting patients as having AD if their expression levels are similar to those of Carr. In some cases, the expression level or expression of at least one inflammasome protein. The parameter representing the level is the expression level of one or more control AD ​​biomarkers. Alternatively, parameters representing the expression level: 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3% If the expression level is within %, 2%, or 1%, then at least one inflammasome protein is expressed. The levels are similar to the expression levels of one or more control AD ​​biomarkers. In some cases, the expression levels of one or more control AD ​​biomarkers were obtained from the patient. Measured in biological samples. In some cases, one or more control ADs are used. The expression levels of biomarkers were obtained from biological samples taken from individuals previously diagnosed with AD. Measured during pull. In some cases, biological data obtained from individuals previously diagnosed with AD. The sample was of the same type as those obtained from patients suspected of having Alzheimer's disease. This is a sample. In some cases, the development of at least one type of inflammasome protein. The current level and the expression levels of one or more control AD ​​biomarkers are the control levels. Expression of at least one inflammasome protein in biological samples obtained from Enhanced levels and expression levels of one or more control AD ​​biomarkers In some cases, biological samples obtained from controls were found to be from individuals suffering from AD. These are the same type of biological samples obtained from patients suspected of having the condition. In this case, the control group consists of healthy individuals, and these healthy individuals exhibit clinical symptoms consistent with Alzheimer's disease (AD). It is an individual that does not exist. In some cases, the development of at least one type of inflammasome protein. The current level and the expression level of one or more control AD ​​biomarkers are at least 1 Regarding inflammasome proteins of various species and one or more control AD ​​biomarkers It is augmented to a predetermined reference value or range of reference values. In some cases, at least It also includes a parameter that represents the expression level of one type of inflammasome protein and one or more co The parameter representing the expression level of control AD ​​biomarkers is the area under the curve (AUC). ) In some cases, patients present with clinical symptoms consistent with AD. In this case, biological samples obtained from patients suspected of having AD are cerebrospinal fluid ( CSF), CNS microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EVs) Yes. In some cases, at least one inflammasome protein and / or one or more The expression levels of the control AD ​​biomarkers above indicate at least one inflammas. Directed towards muproteins and / or one or more control AD ​​biomarkers It is measured by an immunoassay using one or more antibodies. In some cases, less Both inflammasome proteins are interleukin-18 (IL-18), IL -1β, an apoptosis-related speck-like protein containing a caspase recruitment domain (A SC), caspase-1, or a combination thereof. In some cases, at least one type Inflammasome proteins include ASCs. In some cases, at least one type of inflammasome protein. Flamasomal proteins include IL-18. In some cases, one or more controllers... The AD biomarker is neurofilamentous light polypeptide (NFL), soluble It is APP-alpha (sAPPα) and / or soluble APP-beta (sAPPβ). In some cases, at least one inflammasome protein is an ASC, and And one or more control AD ​​biomarkers are soluble APP-alpha (sAPPα ) and the AUC of ASC is 0.833, and the AUC of sAPPα is 0.95 6. In some cases, at least one inflammasome protein is present in the ASC. Yes, and one or more control AD ​​biomarkers are soluble APPβ (sAPPβ ) and the AUC of ASC is 0.833, and the AUC of sAPPβ is 0.91 9. In some cases, at least one inflammasome protein is present in the ASC. Yes, and one or more control AD ​​biomarkers, neurofilament light It is a polypeptide (NFL), and the AUC of ASC is 0.833, and the A of NFL The UC is 0.717. In some cases, the biological sample obtained from the patient is blood. The patient is clear, and the percentage of patients is at least 70%, 75%, 80%, 85%, 90%, 95%. Selected as having AD with 99% or 100% sensitivity and at least 55% specificity. In some cases, the biological sample obtained from the patient is serum, and the patient is At least 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% Selected as having AD at a certain degree. In some cases, biological samples obtained from the patient The substance is serum, and the patient has at least 70% sensitivity and at least 55% specificity. It is selected as having AD. In some cases, the specificity and / or sensitivity is 95% The confidence interval is determined using the receiver operating characteristic (ROC) curve. In some cases, the aforementioned method The law requires the presence of one or more symptoms associated with AD in order to select a patient as having AD. Further includes evaluating the following: In some cases, one or more symptoms associated with AD may be amnesia. Lack of concentration, anxiety, anxiety or confusion when making decisions, difficulty understanding instructions or planning things, difficulty in familiar environments Difficulty moving around at the border, difficulty performing work, forgetting materials immediately after reading them, loss or misplacement of valuable items, Difficulty organizing, confusion of time or place, difficulty controlling bladder or bowel movements, personality or behavior Changes, such as changes in mood or personality, changes in sleep patterns, and communication. Difficulties such as vocabulary problems during conversation or writing, vulnerability to infection, impulsive or unsure judgment, and vision Difficulty understanding images and spatial relationships, misplacing objects and losing the ability to undo steps, impaired judgment. Or it is delinquency, withdrawal from work or social activities. In some cases, at least one type of in Parameters representing the expression level of flammosome proteins and one or more control M The parameter representing the expression level of CI biomarkers is the cutoff value. In this case, at least one inflammasome protein is ASC, and cuto The F value is greater than 264.9 pg / ml and less than 560 pg / ml. In some cases, At least one parameter representing the expression level of one type of inflammasome protein and one or more The parameter representing the expression level of the control MCI biomarker above is the cutoff. It is a value. In some cases, at least one inflammasome protein is present in the ASC. Yes, and the cutoff value is greater than 560 pg / ml.

[0022] In one embodiment, this specification includes the following: a patient has mild cognitive impairment (MCI) or Alzheimer's disease (A A method is provided to determine whether a patient has D), and this method involves obtaining biological information from the patient. To measure the expression level of at least one inflammasome protein in the sample. And the expression level of at least one inflammasome protein in a biological sample A predetermined reference value or range of reference values ​​for at least one inflammasome protein. The comparison is made with the expression level of at least one inflammasome protein being predetermined. If the expression level is within the reference range, AD is indicated, or if the expression level exceeds a predetermined reference value, This includes selecting patients as having MCI. In some cases, at least one type Inflammasome proteins are ASCs. In some cases, the given range of reference values ​​is The range is 264.9 pg / ml to 560 pg / ml. In some cases, the given reference value is It is over 560 pg / ml.

[0023] In another embodiment, this specification describes how to evaluate patients suspected of having age-related macular degeneration (AMD). A method is provided which involves at least one type of biological sample obtained from a patient. Measuring the expression levels of inflammasome proteins and proteins related to AMD The purpose is to determine the presence or absence of a protein signature, where the protein signature is superior To determine that it includes at least one inflammasome protein at elevated levels, If a patient presents with a protein signature, select the patient as having AMD. This includes the following. In some cases, the biological sample obtained from the patient is cerebrospinal fluid (C). SF), CNS microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EVs) In some cases, at least one inflammasome protein is present in the protein signature. The protein level indicates that at least one inflammasome protein is present in the protein signature. It is measured by an immunoassay that uses one or more antibodies directed against protein. In some cases, at least one inflammasome protein is present in the protein signature. Protein levels are determined by the presence of at least one type of protein in the biological sample obtained from the control. It is enhanced against inflammasome protein levels. In some cases, control The biological samples obtained from the rolls were cerebrospinal fluid (CSF), CNS microdialysis fluid, and saliva. These are serum, plasma, urine, or serum-derived extracellular vesicles (EVs). In some cases, control The subject is a healthy individual that does not exhibit clinical symptoms of AMD. In some cases, at least 1 The inflammasome proteins of this species include interleukin-18 (IL-18) and IL-1β. apoptosis-related speck-like proteins (ASCs) containing caspase recruitment domains , caspase-1 or a combination thereof. In some cases, at least one type of insect The ramasome protein contains ASC, and the AUC of ASC is 0.9823. In some cases, at least one inflammasome protein contains IL-18, and IL The AUC at -18 is 0.7286. In some cases, biological samples obtained from patients The sample is serum, and the patient has at least 70%, 75%, 80%, 85%, and 90% of the sample. Selected as having AMD with sensitivity of %, 95%, 99%, or 100%. In this case, the biological sample obtained from the patient is serum, and the patient is at least 70 Sensitivity of %, 75%, 80%, 85%, 90%, 95%, 99%, or 100% and at least It is also selected as having AMD with a specificity of 55%. In some cases, specificity and / or The sensitivity is determined using the receiver operating characteristic (ROC) curve with a 95% confidence interval. In some cases, the method is used to select a patient having AMD, one of which is related to AMD. Further includes evaluating the presence of the above symptoms. In some cases, one related to AMD. The above symptoms include blurred vision, unclear vision, straight lines appearing wavy or distorted, and on printed pages. Blurred areas are visible, difficulty reading or seeing details in low light conditions, visual impairment. Extra perception of bright, dark, or blurred areas in the center of vision; whiteout in the visual center. Or it is a change in color perception. In some cases, at least one inflammasome protein The parameter that represents the level of quality expression is the cutoff value. In some cases, at least Another type of inflammasome protein is ASC, and its cutoff value is 365. The level is greater than 6 pg / mL. In some cases, it is at least one type of inflammasome protein. It is IL-18, and its cutoff value is greater than 242.4 pg / mL.

[0024] In one embodiment, this specification provides a method for treating inflammatory aging in a subject. The law provides a therapeutically effective dose of a monoclonal antibody or antibody flag that specifically binds to ASC. The treatment involves administering the antibody or antibody fragment to the target of the ment, and the antibody or antibody fragment is heavy chain variable (VH) It includes the VH region and the light chain variable (VL) region, and the amino acid sequence of the VH region is the HCDR of SEQ ID NO: 6 1. HCDR2 of sequence number 7 and HCDR3 or HCDR1, HCDR2 and sequence number 8 and / or variants of HCDR3 having at least one amino acid substitution The VL region amino acid sequences include LCDR1 in SEQ ID NO: 12 and LCDR2 in SEQ ID NO: 13. and LCDR3 or LCDR1, LCDR2 and / or LCDR3 of sequence number 14 The administration of variants having at least one amino acid substitution is included. This treats inflammatory aging in the subject. In some cases, monoclonal antibodies Alternatively, the amino acid sequence of the VH region of the antibody fragment is SEQ ID NOs: 18, 19, 20, 21 , less than 22 or the amino acid sequence of sequence numbers 18, 19, 20, 21 or 22 Both contain 95%, 96%, 97%, 98%, or 99% identical amino acid sequences, and mono The amino acid sequence of the VL region of the ronal antibody or its antibody fragment is shown in SEQ ID NOs. 28, 29. , 30, 31 or less than the amino acid sequence of sequence numbers 28, 29, 30 or 31 They all contain 95%, 96%, 97%, 98%, or 99% identical amino acid sequences. In that case, the amino acid sequence of the VH region of the monoclonal antibody or its antibody fragment is At least 95%, 96%, and 97% of the amino acid sequence of sequence number 18 or sequence number 18 , containing 98% or 99% identical amino acid sequences, monoclonal antibody or antibody f The amino acid sequence of the VL region of the lagment is the same as the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28. In contrast, if at least 95%, 96%, 97%, 98%, or 99% of the amino acid sequence is identical Includes. In some cases, the VH region amino of a monoclonal antibody or its antibody fragment. The acid sequence is at least 95% of the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 18. Contains 6%, 97%, 98%, or 99% identical amino acid sequences, and is a monoclonal antibody or The amino acid sequence of the VL region of that antibody fragment is the same as in SEQ ID NO: 29 or SEQ ID NO: 29. At least 95%, 96%, 97%, 98%, or 99% of the amino acid sequence is identical. Contains a monooxidative sequence. In some cases, the V of a monoclonal antibody or its antibody fragment. The H region amino acid sequence is at least the same as SEQ ID NO: 18 or the amino acid sequence of SEQ ID NO: 18. It also contains 95%, 96%, 97%, 98%, or 99% identical amino acid sequences, and is monochromatic. The VL region amino acid sequence of a non-alcoholic antibody or its antibody fragment is as shown in SEQ ID NO: 30 or the sequence... For amino acid sequence number 30, at least 95%, 96%, 97%, 98%, or 9% Contains 9% identical amino acid sequences. In some cases, monoclonal antibodies or their antibody fragiles. The amino acid sequence of the VH region of the ligment is the same as the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 18 and contain at least 95%, 96%, 97%, 98%, or 99% identical amino acid sequences. Furthermore, the amino acid sequence of the VL region of a monoclonal antibody or its antibody fragment is the sequence number. At least 95%, 96%, 97%, and 98% of the amino acid sequence of 31 or SEQ ID NO: 31. Contains % or 99% identical amino acid sequences. In some cases, monoclonal antibodies or The amino acid sequence of the VH region of that antibody fragment is the same as SEQ ID NO: 19 or SEQ ID NO: 19. At least 95%, 96%, 97%, 98%, or 99% of the amino acids are identical to the no-acid sequence. The amino acid sequence of the VL region of a monoclonal antibody or its antibody fragment, which includes an anoic acid sequence. This is at least 95%, 96%, of the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28. It contains 97%, 98%, or 99% identical amino acid sequences. In some cases, monoclonal The amino acid sequence of the VH region of the NAL antibody or its antibody fragment is SEQ ID NO: 19 or sequence number At least 95%, 96%, 97%, 98%, or 99% of the amino acid sequence of No. 19. % Contains the same amino acid sequence, and the VL region amino acid sequence is SEQ ID NO: 29 or SEQ ID NO: 29 The amino acid sequence is identical by at least 95%, 96%, 97%, 98%, or 99%. It contains the amino acid sequence of a monoclonal antibody or its antibody fragment. The amino acid sequence of the VH region is less than that of SEQ ID NO: 19 or the amino acid sequence of SEQ ID NO: 19. It contains at least 95%, 96%, 97%, 98%, or 99% of the same amino acid sequence, mono The amino acid sequence of the VL region of a clonal antibody or its antibody fragment is as shown in SEQ ID NO: 30 or At least 95%, 96%, 97%, 98% or more of the amino acid sequence of SEQ ID NO: 30 They contain 99% identical amino acid sequences. In some cases, monoclonal antibodies or their antibodies The amino acid sequence of the VH region of the fragment is the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 19. For at least 95%, 96%, 97%, 98%, or 99% of the amino acid sequence is identical. The amino acid sequence of the VL region of the monoclonal antibody or its antibody fragment is the sequence For the amino acid sequence of number 31 or sequence number 31, at least 95%, 96%, 97%, Contains 98% or 99% identical amino acid sequences. In some cases, monoclonal antibodies. Alternatively, the amino acid sequence of the VH region of the antibody fragment is the same as SEQ ID NO: 20 or SEQ ID NO: 20 At least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence. Amino acid sequence, including the VL region amino acids of a monoclonal antibody or its antibody fragment. The sequence is at least 95% and 96% relative to the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28. Contains %, 97%, 98%, or 99% identical amino acid sequences. In some cases, the VH region The regional amino acid sequence is at least 9 relative to SEQ ID NO: 20 or the amino acid sequence of SEQ ID NO: 20. Contains 5%, 96%, 97%, 98%, or 99% identical amino acid sequences, VL region amino acids The amino acid sequence is at least 95% of the amino acid sequence of SEQ ID NO. 29 or SEQ ID NO. 29. It contains 96%, 97%, 98%, or 99% identical amino acid sequences. In some cases, The amino acid sequence of the VH region of a noclonal antibody or its antibody fragment is as shown in SEQ ID NO: 20 or This is at least 95%, 96%, 97%, 98% of the amino acid sequence of SEQ ID NO: 20 or containing 99% identical amino acid sequences, monoclonal antibodies or their antibody fragments The VL region amino acid sequence is less than that of SEQ ID NO: 30 or the amino acid sequence of SEQ ID NO: 30. They all contain 95%, 96%, 97%, 98%, or 99% identical amino acid sequences. In that case, the amino acid sequence of the VH region of the monoclonal antibody or its antibody fragment is At least 95%, 96%, and 97% of the amino acid sequence of sequence number 20 or sequence number 20 , containing 98% or 99% identical amino acid sequences, monoclonal antibody or antibody f The amino acid sequence of the VL region of the lagment is the same as the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 31. In contrast, if at least 95%, 96%, 97%, 98%, or 99% of the amino acid sequence is identical Includes. In some cases, the VH region amino of a monoclonal antibody or its antibody fragment. The acid sequence is at least 95% of the amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 21. Contains 6%, 97%, 98%, or 99% identical amino acid sequences, and is a monoclonal antibody or The VL region amino acid sequence of the antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 28 or the amino acid sequence of SEQ ID NO: 28 and contains an amino acid sequence. In some cases, the VH region amino acid sequence is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 21 or the amino acid sequence of SEQ ID NO: 21 and contains an amino acid sequence. The VL region amino acid sequence is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 29 or the amino acid sequence of SEQ ID NO: 29 and contains an amino acid sequence. In some cases, the VH region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 21 or the amino acid sequence of SEQ ID NO: 21 and contains an amino acid sequence. The VL region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 30 or the amino acid sequence of SEQ ID NO: 30 and contains an amino acid sequence. In some cases, the VH region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 21 or the amino acid sequence of SEQ ID NO: 21 and contains an amino acid sequence. The VL region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 31 or the amino acid sequence of SEQ ID NO: 31 In some cases, the VH region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 22 or the amino acid sequence of SEQ ID NO: 22 and contains an amino acid sequence. The VL region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 30 or the amino acid sequence of SEQ ID NO: 30 and contains an amino acid sequence. In some cases, the VH region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 21 or the amino acid sequence of SEQ ID NO: 21 and contains an amino acid sequence. The VL region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 31 or the amino acid sequence of SEQ ID NO: 31 In some cases, the VH region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 21 or the amino acid sequence of SEQ ID NO: 21 and contains an amino acid sequence. The VL region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 31 or the amino acid sequence of SEQ ID NO: 31 and contains an amino acid sequence. In some cases, the VH region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 22 or the amino acid sequence of SEQ ID NO: 22 and contains an amino acid sequence. In some cases, the VH region amino acid sequence of the monoclonal antibody or its antibody fragment is at least 95%, 9%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 22 or the amino acid sequence of SEQ ID NO: 22 and contains an amino acid sequence. Amino acid sequence, including the VL region amino acids of a monoclonal antibody or its antibody fragment. The sequence is at least 95% and 96% relative to the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28. Contains %, 97%, 98%, or 99% identical amino acid sequences. In some cases, monochromatic The amino acid sequence of the VH region of a ronal antibody or its antibody fragment is as shown in SEQ ID NO. 22 or For the amino acid sequence of column number 22, at least 95%, 96%, 97%, 98%, or Contains 99% identical amino acid sequences, and is the VL of a monoclonal antibody or its antibody fragment. The regional amino acid sequence is at least the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 29 Contains 95%, 96%, 97%, 98%, or 99% identical amino acid sequences. In this case, the amino acid sequence of the VH region of the monoclonal antibody or its antibody fragment is the sequence number At least 95%, 96%, 97%, and 9% of the amino acid sequence of number 22 or sequence number 22. A monoclonal antibody or its antibody flag containing 8% or 99% identical amino acid sequences. The VL region amino acid sequence of ment is compared to SEQ ID NO: 30 or the amino acid sequence of SEQ ID NO: 30. and contain at least 95%, 96%, 97%, 98%, or 99% identical amino acid sequences. In some cases, the VH region amino acid distribution of a monoclonal antibody or its antibody fragment The column is at least 95% or 96% of the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 22. , containing 97%, 98%, or 99% identical amino acid sequences, monoclonal antibody or so The VL region amino acid sequence of the antibody fragment is the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 31 At least 95%, 96%, 97%, 98%, or 99% of the amino acids in the acid sequence are identical. Contains an acid sequence. In some cases, ASC is the human ASC protein. In some cases The combined antibody fragment is Fab, F(ab')2, Fab', scFv, single domain. Antibodies, diabolic antibodies, or single-stranded camelid antibodies. In some cases, monoclonal antibodies. The body or its antibody fragments are human, humanized, or chimeric. In some cases, mono Administering clonal antibodies or their antibody fragments is at least effective in treating inflammatory cytotoxicity. Reduces the level of the antibody. In some cases, monoclonal antibodies or their antibody fragments Administration of [substance] results in inhibition of inflammasome activation in the subject. In some cases, Administration of monoclonal antibodies or their antibody fragments compared to controls resulted in ASC This results in a reduction of activity. In some cases, the control group is untreated. In such cases, administration is by intraventricular, intraperitoneal, intravenous, or inhalation. [Brief explanation of the drawing]

[0025] [Figure 1A-1D] This illustrates the elevated levels of inflammasome proteins in the serum of MS patients. Protein levels in pg / ml for caspase-1 (Figure 1A), ASC (Figure 1B), IL-1β (Figure 1C), and IL-18 (Figure 1D) in serum samples from MS patients and healthy donors. Significant p-values ​​are shown above each box plot. Boxes and whiskers are indicated at the 5th and 95th percentiles. Caspase-1: N=9 control and 19 MS, ASC: N=115 control and 32 MS, IL-1β: N=21 control and 8 MS, and IL-18: N=119 control and 32 MS. [Figure 2A-2D] ROC curves for caspase-1 (Figure 2A), ASC (Figure 2B), IL-1β (Figure 2C), and IL-18 (Figure 2D) from serum samples of MS and healthy donors are shown as examples. [Figure 3]Examples of inflammasome proteins in serum as biomarkers for MS are presented. ROC curves for caspase-1, ASC, IL-1 beta, and IL-18. Caspase-1: N=9 control and 19 MS; ASC: N=115 control and 32 MS; IL-1 beta: N=21 control and 8 MS; IL-18: N=119 control and 32 MS. [Figure 4] A table illustrating the characteristics of the target population for multiple sclerosis (MS) from Example 1 is provided. [Figures 5A-5D] This illustrates the elevated levels of inflammasome proteins in the serum of stroke patients. Protein levels in pg / ml for caspase-1 (Figure 5A), ASC (Figure 5B), IL-1 beta (Figure 5C), and IL-18 (Figure 5D) in serum samples from stroke patients and healthy donors. Significant p-values ​​are shown above each box plot. Boxes and whiskers are indicated at the 5th and 95th percentiles. NS = not significant. Caspase-1: N=8 controls and 13 strokes, ASC: N=75 controls and 16 strokes, IL-1 beta: N=9 controls and 8 strokes, and IL-18: N=79 controls and 15 strokes. [Figure 6] Examples of serum inflammasome proteins as biomarkers for stroke are presented. ROC curves for caspase-1, ASC, IL-1 beta, and IL-18. Caspase-1: N=8 controls and 13 strokes; ASC: N=75 controls and 16 strokes; IL-1 beta: N=9 controls and 8 strokes; and IL-18: N=79 controls and 15 strokes. [Figure 7A-7C]Figure 7A illustrates a comparison of total protein levels from serum-derived extracellular vesicles (EVs). Bradford assays were performed after EV isolation from serum to determine the total protein concentration in isolates obtained using the Invitrogen Kit (INVTR) and ExoQuick Kit (EQ). Data are presented as mean ± SEM. N=6 / group. Figure 7B depicts a representative image of total loaded protein. Stain-free image of serum-derived EV protein. Equal volumes of protein lysate (10 ml) were loaded into each lane of the Criterion gel. Figure 7C depicts a bar graph showing the quantification of the entire lane corresponding to loaded EVs isolated by the Invitrogen Kit (INV) and ExoQuick Kit (EQ). [Figures 8A-8F] This illustrates the characterization of extracellular viable cells (EVs) in serum from stroke patients. Figure 8A shows representative immunoblots of CD81 and NCAM-positive EVs isolated by the Invitrogen kit (IN) and ExoQuick kit (EQ). +Contr: Positive control of isolated EVs. Quantification of CD81 (Figure 8B) and NCAM (Figure 8C)-positive EVs isolated from serum by the Invitrogen kit (INV) and ExoQuick kit (EQ). Figure 8D shows electron microscope images of EVs isolated by two different techniques. Bar = 100 nm. Nanoparticle tracking analysis / particle size distribution of isolated serum-derived EVs. Nanoparticle tracking analysis predicts the particle size distribution and concentration in serum-derived EV samples isolated by the Invitrogen kit (Figure 8E) and ExoQuick kit (Figure 8F). [Figures 9A-9C] This example illustrates the elevation of ASC in serum-derived extravasation cells (EVs) from stroke patients. Protein levels in pg / ml for ASC (Figure 9A), IL-1 beta (Figure 9B), and IL-18 (Figure 9C) in serum-derived EVs from stroke patients and healthy donors. Significant p-values ​​are shown above each box plot. Boxes and whiskers are indicated at the 5th and 95th percentiles. NS = not significant. ASC: N=16 controls and 16 strokes, IL-1 beta: N=10 controls and 9 strokes, and IL-18: N=16 controls and 13 strokes. [Figure 10]Illustrate inflammasome proteins in serum-derived EVs as biomarkers for stroke. ROC curves of ASC, IL-1 beta, and IL-18. ASC: N = 16 controls and 16 strokes, IL-1 beta: N = 10 controls and 9 strokes, and IL-18: N = 16 controls and 13 strokes. [Figure 11] Illustrate a table containing the characteristics of stroke subjects from Example 2. [Figures 12A-12D] Illustrate the ROC curves of caspase-1 (Figure 12A), ASC (Figure 12B), IL-1 beta (Figure 12C), and IL-18 (Figure 12D) from serum samples of stroke and healthy donors. [Figures 13A-13F] Illustrate the characterization of inflammasome proteins in serum-derived EVs. Figure 13A depicts a representative image of immunoblot analysis of inflammasome proteins in EVs from serum. Quantification of immunoblot analysis of (Figure 13B) NLRP3, (Figure 13C) caspase-1, (Figure 13D) ASC, (Figure 13E) IL-1 beta, and (Figure 13F) IL-18 in EVs derived from serum using Invitrogen kit (IN) and ExoQuick kit (EQ). Data presented as mean ± SEM. N = 6 / group. *p < 0.05. [Figure 14A-14C] Illustrate the ROC curves of ASC (Figure 14A), IL-1 beta (Figure 14B), and IL-18 (Figure 14C) from serum-derived extracellular vesicles of stroke and healthy donors. [Figures 15A-15D] Illustrate how inflammasome proteins increase in the serum of TBI patients. Protein levels in pg / ml of ASC (Figure 15A), caspase-1 (Figure 15B), IL-18 (Figure 15C), and IL-1β (Figure 15D) in serum samples from TBI patients and healthy donors (controls). ASC: N = 120 controls, 20 TBI. Caspase-1: N = 11 controls, 19 TBI. IL-18: N = 120 controls, 21 TBI. IL-1β: N = 25 controls, 10 TBI. Boxes and whiskers are shown at the 5th and 95th percentiles. *p < 0.05. [Figures 16A-16D]ROC curves for caspase-1 (Figure 16A), ASC (Figure 16B), IL-1β (Figure 16C), and IL-18 (Figure 16D) from serum samples of TBI patients and healthy donors are shown as examples. [Figures 17A-17B] This illustrates how inflammasome proteins are elevated in CSF from TBI patients. Protein levels in pg / ml for ASC (Figure 17A) and IL-18 (Figure 17B) in CSF samples from TBI patients and healthy donors (controls). ASC: N=21 control, 15 TBIs. IL-18: N=24 control, 16 TBIs. Boxes and whiskers are shown at the 5th and 95th percentiles. *p<0.05. [Figures 18A-18B] ROC curves for ASC (Figure 18A) and IL-18 (Figure 18B) from CSF samples from TBI patients and healthy donors are shown as examples. [Figures 19A-19C] Inflammasome proteins are exemplified as predictive biomarkers for TBI. Protein levels in pg / ml for caspase-1 (Figure 19A), ASC (Figure 19B), and IL-18 (Figure 19C) in serum samples from TBI patients. Groups were divided into good and poor outcomes based on GOSE. Significance p-values ​​are shown above each box plot. Boxes and whiskers are indicated at the 5th and 95th percentiles. Caspase-1: N=4 good and 16 poor, ASC: N=5 good and 16 poor, and IL-18: N=5 good and 16 poor. [Figures 20A-20B] The ROC curves for ASC outcomes (good vs. poor) from the second (Figure 20A) and fourth (Figure 20B) samplings are shown as examples. [Figures 21A-21D]This illustrates the elevated levels of inflammasome proteins in the serum of MCI and AD patients. Protein levels in pg / ml for ASC (Figure 21A), caspase-1 (Figure 21B), IL-18 (Figure 21C), and IL-1 beta (Figure 21D) in serum samples from MCI, AD patients, and age-matched healthy donors (controls). * represents the p-value of significance compared to the control, and ** represents the p-value of significance between MCI and AD. ASC: N=66 control, 32 MCI, 31 AD. Caspase-1: N=7 control, 23 MCI, 15 AD. IL-18: N=69 control, 31 MCI, 32 AD. IL-1 beta: N=9 control, 9 MCI, 8 AD. Boxes and whiskers are indicated at the 5th and 95th percentiles. ***p<0.05. [Figures 22A-22D] ROC curves for ASC (Figure 22A), caspase-1 (Figure 22B), IL-18 (Figure 22C), and IL-1 beta (Figure 22D) from serum samples of MCI and age-matched healthy donors are shown as examples. [Figure 23A] Inflammasome proteins in serum are shown as biomarkers for MCI. The ROC curves for caspase-1, ASC, IL-1 beta, and IL-18 from Figures 22A-22D are superimposed on a single graph. [Figure 23B] This example illustrates serum inflammasome proteins as biomarkers for Alzheimer's disease (AD). ROC curves for caspase-1, ASC, IL-1 beta, and IL-18 from serum samples of AD and age-matched healthy donors are superimposed on a single graph. [Figure 23C] This example illustrates inflammasome proteins in serum as biomarkers for MCI. ROC curves for caspase-1, ASC, IL-1 beta, and IL-18 from serum samples of AD and MCI are superimposed on a single graph. [Figures 24A-24C]Examples of elevated proteins in the serum of MCI and AD patients are shown. Protein levels in pg / ml for sAPPα (Figure 24A), sAPPβ (Figure 24B), and NFL (Figure 24C) in serum samples from MCI, AD patients, and age-matched healthy donors (controls). [Figure 25A] This example illustrates serum inflammasome proteins as biomarkers for MCI. ROC curves for NFL, sAPPα, sAPPβ, and ASC from serum samples of MCI and age-matched healthy donors are superimposed on a single graph. [Figure 25B] This example illustrates serum inflammasome proteins as biomarkers for Alzheimer's disease (AD). ROC curves for NFL, sAPPα, sAPPβ, and ASC from serum samples of MCI and age-matched healthy donors are superimposed on a single graph. [Figure 25C] This example illustrates serum inflammasome proteins as biomarkers for MCI. ROC curves for NFL, sAPPα, sAPPβ, and ASC from serum samples of MCI and AD are superimposed on a single graph. [Figure 26A] A linear regression analysis between IL-18 and ASC protein levels is presented as an example. [Figure 26B] This example illustrates the logarithmic transformation of a linear regression analysis between IL-18 and ASC protein levels. [Figure 26C] A linear regression analysis between the levels of sAPPα and sAPPβ is presented as an example. [Figure 26D] This example illustrates the logarithmic transformation of a linear regression analysis between the protein levels of sAPPα and sAPPβ. [Figure 26E] This example illustrates the fitting of a linear regression analysis between IL-18 and ASC protein levels. [Figure 26F] This example illustrates the fitting of a logarithmic transformation to a linear regression analysis between IL-18 and ASC protein levels. [Figure 26G] The results of residual analysis from linear regression analysis between IL-18 and ASC protein levels are illustrated as an example. [Figure 26H]The results of residual analysis obtained by logarithmically transforming linear regression analysis between IL-18 and ASC protein levels are illustrated as an example. [Figure 26I] This example illustrates the fitting of a linear regression analysis between the protein levels of sAPPα and sAPPβ. [Figure 26J] This example illustrates the fitting of a logarithmic transformation to a linear regression analysis between the protein levels of sAPPα and sAPPβ. [Figure 26K] The results of residual analysis from linear regression analysis between protein levels of sAPPα and sAPPβ are shown as an example. [Figure 26L] The results of residual analysis obtained by logarithmically transforming linear regression analysis between protein levels of sAPPα and sAPPβ are illustrated as an example. [Figure 27A] Cluster analysis is illustrated using ASC protein levels in controls, MCI, and AD patients. Clustering is shown using Gaussian mixture modeling. [Figure 27B] Cluster analysis using ASC protein levels in controls, MCI, and AD patients is illustrated. Cluster dendrograms are shown. [Figure 27C] Cluster analysis using ASC protein levels in controls, MCI, and AD patients is illustrated. A coordinate plot is shown. [Figures 28A-28D] This illustrates the elevated levels of inflammasome proteins in the serum of AMD patients. Protein levels in pg / ml for ASC (Figure 28A), caspase-1 (Figure 28B), IL-18 (Figure 28C), and IL-1 beta (Figure 28D) in serum samples from AMD patients are shown. [Figures 29A-29D] ROC curves for ASC (Figure 29A), caspase-1 (Figure 29B), IL-18 (Figure 29C), and IL-1 beta (Figure 29D) from serum samples of AMD donors are shown as examples. [Figures 30A-30D] The expression of inflammasome protein ASC (Figure 30A), caspase-1 (Figure 30B), IL-18 (Figure 30C), and IL-1 beta (Figure 30D) in wet and dry AMD patients is illustrated. [Figure 31]This paper provides an example of residual analysis results from linear regression analysis between ASC and IL-18 protein levels in AMD patients. [Figure 32] This example illustrates the binary logistic regression of ASC protein levels in serum from patients with and without an AMD diagnosis. [Figure 33] This example illustrates the binary logistic regression of IL-18 protein levels in the serum of patients with and without an AMD diagnosis. [Figure 34] This study illustrates how a monoclonal antibody against ASC (i.e., IC-100 (mAb)) inhibits IL-1 beta activation in the cortex of aged mice. Mice were treated with IC-100 (5 mg / kg) and saline control (ip) and sacrificed after 3 days. Immunoblots of cortical protein lysates from young (3 months) and aged (18 months) mice blotted against IL-1 beta. Data presented as mean ± SEM. 3m: 3 months old, 18m: 18 months old. Sal: saline. N=6 / group. *p<0.05. [Figures 35A-35D] This study illustrates how a monoclonal antibody against ASC (i.e., IC-100(MAb)) inhibits NLRP1 inflammasome activation in the cortex of aged mice. Mice were treated with IC-100 (5 mg / kg) and saline control (ip) and sacrificed after 3 days. Figure 35A shows representative immunoblots of cortical protein lysates from young (3-month-old) and aged (18-month-old) mice blotted against NLRP1, caspase-1, and ASC, while Figures 35B-35D show the relative concentrations of NLRP1 (Figure 35B), caspase-1 (Figure 35C), and ASC (Figure 35D) as determined from representative immunoblots, including the immunoblots shown in Figure 35A. Data are presented as mean ± SEM. 3m: 3 months old, 18m: 18 months old. Sal: saline. N=6 / group. *p<0.05. [Figures 36A-36C]This study illustrates how a monoclonal antibody against ASC (i.e., IC-100(MAb)) inhibits non-canonical inflammasome activation in the cortex of aged mice. Mice were treated with IC-100 (5 mg / kg) and saline control (ip) and sacrificed after 3 days. Figure 36A shows representative immunoblots of cortical protein lysates from young (3-month-old) and aged (18-month-old) mice blotted against caspase-8 and caspase-11, while Figures 36B-36C show the relative concentrations of caspase-8 (Figure 36B) and caspase-11 (Figure 35C) as determined from representative immunoblots, including the immunoblots shown in Figure 36A. Data are presented as mean ± SEM. 3m: 3 months old, 18m: 18 months old. Sal: saline. N=6 / group. *p<0.05. [Figure 37] This study illustrates the formation of a non-canonical NLRP1-ASC-caspase-8 inflammasome in the cortex of aged mice. Co-immunoprecipitation (IP) of cortical protein lysates from aged (18 months of age, treated with saline and IC-100) and young (3 months of age) mice with IC-100 (anti-ASC) and blotting for ASC, caspase-8, NLRP1, and caspase-1 suggested protein-protein interactions between these proteins. 3m: 3 months of age, 18m: 18 months of age. Sal: saline. [Figure 38] The results of a linear regression analysis between ASC and the pro-inflammatory cytokine IL-18 are shown. [Figure 39] The results of the residual analysis to evaluate the fit of the linear model are shown. [Figure 40] The estimated coefficients for ASC are shown according to a binary logistic regression of ASC protein levels in serum from patients with and without an AMD diagnosis. [Figure 41] The estimated coefficients for IL-18 are shown according to a binary logistic regression of ASC protein levels in serum from patients with and without an AMD diagnosis. [Figures 42A-42D]The expression of inflammasome proteins ASC (Figure 42A) and IL-18 (Figure 42B), as well as known NASH biomarkers Gal-3 (Figure 42C) and C-reactive protein (CRP, Figure 42D), from serum samples of NASH patients is illustrated. [Figures 43A-43D] ROC curves for ASC (Figure 43A), IL-18 (Figure 43B), Gal-3 (Figure 43C), and C-reactive protein (Figure 43D) from serum samples of NASH donors are shown as examples. [Figure 44] Examples of serum inflammasome proteins as biomarkers for NASH are shown. The ROC curves for IL-18, ASC, and Gal-3 from Figures 43A-43C are superimposed on a single graph. [Modes for carrying out the invention]

[0026] definition Unless otherwise defined, all technical terms used herein refer to the technology to which this invention belongs. It has the same meaning as that ordinarily understood by those skilled in the field.

[0027] The section headings used in this specification are for structural purposes only and do not describe the content. It should not be interpreted as limiting the subject matter. It is not limited, but patents, patents This specification includes patent applications, papers, books, and specialized publications, as well as any other documents or parts thereof. All of these are expressly incorporated herein by reference for all purposes. If a term is defined in one or more of the cited documents or parts thereof, and the definition of that term in this application is as follows: In case of any conflict, the definitions set forth herein shall prevail. However, references cited herein shall prevail. References, articles, publications, patents, patent publications, and patent applications all, by reference thereto, To constitute valid prior art or to form part of common general knowledge in any country in the world This does not mean that we have endorsed such things, nor can it be considered that we have made any kind of recommendation. It should not be. Compositions and methods similar to or equivalent to those described herein are part of the present invention. The following are preferred compositions and methods that can be used for implementation or testing.

[0028] The terms "a" or "an" refer to more than one of the entities. See above. That is, it is possible to refer to multiple references. For this reason, "one (a) The terms "one (an)", "one or more", and "at least one" are used in this specification. In writing, they are used interchangeably. In addition, the indefinite article "a" or "an" The reference to an "element" by this means that the context clearly requires that only one element exists. Unless otherwise specified, the possibility of two or more elements being present is not ruled out.

[0029] Unless otherwise required by context, throughout this specification and the claims, the term "including ( The word "comprise)" and its variations, for example, "comprises". And "includes" in an open, inclusive sense, that is, "not limited to" It should be interpreted as "not, but includes." The use of substitutes (e.g., "or") It should be understood to mean one of the substitutes, all of them, or any combination thereof. In this specification, the terms “about” and “essentially derived from” are used in particular. Unless otherwise specified, this means ±20% of the indicated range, value, or structure.

[0030] Throughout this specification, any reference to “one embodiment” or “a certain embodiment” is to this embodiment and Certain features, structures, or properties described in relation to this disclosure are included in at least one embodiment of this disclosure. This means that it may be rare. Therefore, throughout this specification, in various places, "one embodiment" The appearance of the phrases "then" or "in one embodiment" does not necessarily mean that all embodiments are the same. This does not necessarily refer to the following. The specific embodiments discussed below are merely examples and not limited to the above. This is not intended to be definitive. For clarity, the information in this disclosure is described in relation to separate embodiments. It can be seen that certain features can be combined and provided in a single embodiment. Conversely, concise To ensure clarity, the various features of this disclosure described in relation to a single embodiment may be described separately or individually. Such a suitable partial combination may also be provided.

[0031] Throughout this disclosure, various aspects of the methods and compositions provided herein are within the scope of this disclosure. - Can be presented in matte format. The use of a range format is simply for convenience and conciseness. It should be understood that this is merely a construct and is inflexible within the scope of the present invention. It should not be interpreted as a limitation. Therefore, the description of the scope should include all possible parts within that scope. It should be considered that the entire scope and individual figures have been specifically disclosed. The ranges indicated as 1-6 are different from ranges such as 1-3, 1-4, 1-5, 2-4, 2-6, 3-6, etc. A partial range and specific numbers within that range, for example, 1, 2, 3, 4, 5, and 6, are specifically opened. It should be considered as indicated. This applies regardless of the scope.

[0032] As used herein, "protein" and "polypeptide" refer to the length or post-translational length. Regardless of modifications, such as glycosylation or phosphorylation, any peptide-linked amino acid It is used synonymously to mean a chain.

[0033] As used herein, the term "antibody" generally and broadly means "immunoglobulin." The immunoactive portion or fragment of phospholipid (Ig) molecules and immunoglobulin molecules, In other words, they specifically bind to antigens (e.g., ASC, NLRP1, AIM2, etc.) This refers to a molecule containing an antigen-binding site (which reacts with an immune response). The antibodies provided herein These are polyclonal antibodies and monoclonal antibodies (mAbs) that can be labeled in soluble or conjugated form. ), chimeric antibodies, humanized antibodies, anti-idiotypic (anti-Id) antibodies against antibodies and so These may be active fragments, regions, or derivatives. The antibodies used herein are It may be a chimera, humanized, or of human origin.

[0034] "To bind specifically to ~" or "to have an immune reaction with ~" means that an antibody specifically binds to one of the desired antigens. This means that it reacts with the antigenic determinant above and does not react with other polypeptides. Specific implementation Morphologically, antibodies are complex mixtures of proteins and / or macromolecules that dominate their target antigens. It is said that when it recognizes an antigen, it specifically binds to it. The term "antibody" is used in a broad sense. It generally consists of four polypeptide chains, namely two heavy (H) chains and two light (L) chains. It contains immunoglobulin (Ig) molecules or retains the intrinsic target-binding feature of Ig molecules. This refers to any of those functional fragments, variants, variants, or derivatives. Antibody formats of such variants, derivatives, or variants are known in the art. The anti-ASC and anti-NLRP1 antibodies of the present invention are, respectively, ASC and NLRP1 It has the ability to bind to a specific part and interferes with caspase-1 activation.

[0035] As used herein, the term "humanized antibody" refers to the minimal portion of a non-human antibody. This refers to antibodies that have been introduced into other human antibodies.

[0036] As used herein, the term "human antibody" refers to a very minor sequence change or With variations, virtually every part of the protein in humans is virtually immune. This refers to antibodies that are virulent.

[0037] In full-length antibodies, each heavy chain has a heavy chain variable region (abbreviated as HCVR or VH in this specification). ) and the heavy chain constant region. The heavy chain constant region consists of three domains CH1, CH2 and CH3 Each light chain includes a light chain variable region (abbreviated herein as LCVR or VL) and a light It includes a chain constant region. The light chain constant region contains one domain CL. The VH and VL regions are A complementary determination region in which a more conserved region called the framework region (FR) intervenes. It can be further subdivided into a highly variable region called CDR. Each VH and VL is an amino powder. From end to carboxyl terminus, in the following order: FR1, CDR1, FR2, CDR2, FR3, C It consists of three CDRs and four FRs arranged in DR3 and FR4. The molecule is of any type (e.g., IgG, IgE, IgM, IgD, IgA and I IgA1 and IgA1 are classes (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA1). IgG, IgD, and IgE antibodies are generally two types of antibodies. A single heavy chain and two identical light chains, as well as a heavy chain variable region (VH) and a light chain variable region (VL) in each. It contains two antigen-binding domains composed of each monomer. Generally, IgA antibodies contain each monomer It is composed of two heavy chains and two light chains (as in the case of IgG, IgD, and IgE antibodies). (2) It is composed of two monomers, and thus the IgA molecule is, in this case, VH and VL respectively. It has four antigen-binding domains composed of two heavy chains and two It is monomeric in that it is composed of one light chain. Secretory IgM antibodies are generally monomeric. A nomer consists of two heavy chains and two light chains (as in the case of IgG and IgE antibodies). It is composed of five monomers. Thus, the IgM molecule is, in this case as well, VH and VL. It has 10 antigen-binding domains composed of [IgM]. Cell surface form IgM is also present, which is I It has a two-heavy-chain / two-light-chain structure similar to γ, IgD, and IgE antibodies.

[0038] The term "antigen-binding fragment" or "antigen-binding moiety" as used herein refers to an antigen. The terms "binding site," "binding domain," or "binding region" refer to an antigen (for example, Antibody proteins and polypeptides that possess the ability to specifically bind to ASC proteins. , the domain, region, part or site of an oligopeptide or peptide, i.e., antibody-derived peptide This can mean a binding domain. The exemplary binding domain is the variable region of a single-chain antibody (for example, Includes the main antibody (sFv, scFv, scFab) and the antibody portion (e.g., domain antibody). Fusion protein, receptor ectodomain and ligand (e.g., cytokine, chemocytogen) (Includes n). In one embodiment, the fusion protein includes one or more CDRs. Another embodiment Morphologically, the fusion protein consists of CDR H3 (VH CDR3) and / or CDR L3 (VL CDR3) is included. For the purposes of the present invention, the fusion protein is one or more antibodies, Additional amino acid sequences, for example, attached to the N-terminus or C-terminus of an antibody or its antibody fragment. It contains non-homologous or homologous sequences from another region. However, this is not limited to "tags" such as FLAG tags or 6His tags, or blood. Examples include enzymes or polypeptides that increase the half-life of the antibody contained within. The tag indicates this technology. It is well known in the field. Additional amino acid sequences are polyparticles containing 1 to 100 or more residues. Amino and / or carboxyl terminus fusions and single fusions that may be within the length range of a peptide. Alternatively, it may include the insertion of multiple amino acid residues into the sequence.

[0039] The antigen-binding site is generally one of six surface polypeptides called complementarity-determining regions (CDRs). The heavy chain variable region (VH) including the antigen-binding interface formed by the thyroid loop and The framework can be formed by the light chain variable region (VL) immunoglobulin domain. VH (HCDR1, HCDR2, HCDR3) and VL (LCDR) with region (FR) 1. There are three CDs in each of the LCDR2 and LCDR3. In a particular embodiment, The binding domain contains or consists of an antigen-binding site (for example, a variable heavy chain sequence and Includes a variable light chain sequence or alternative framework regions (FRs) (e.g., one or more A Three light chain complementarity determining regions (C) of an antibody placed within a human FR (which optionally contains a mino acid substitution) (Includes DR and three heavy-chain CDRs).

[0040] The terms "CDR area" or "CDR" were defined in Kabat et al., 1991. Kabat, EA et al., (1991) Sequences of Prot. eins of Immunological Interest,5th Editi on.US Department of Health and Human Ser. (Vices, Public Service, NIH, Washington) and its This may refer to the hypervariable region of the heavy or light chain of an immunoglobulin as defined in subsequent editions. It typically contains three heavy chain CDRs and three light chain CDRs.

[0041] It has been shown that the antigen-binding function of antibodies can be performed by fragments of full-length antibodies. Embodiments of antibodies and antibody fragments are bispecific, tripspecific, and dual specific. It may also be a multispecific format that specifically binds to heterologous or two or more different antigens. Examples of binding fragments included in the term "antigen-binding fragment" of antibodies. (i) Fab fragment (W) consisting of VL, VH, CL and CH1 domains ard,ESet al.,(1989)Nature 341,544-546) (ii) Fd fragment consisting of VH and CH1 domains (McCafferty et al., (1990) Nature, 348, 552-554), (iii) single Fv fragment consisting of the VL and VH domains of the antibody (Holt et al., (2 003)Trends in Biotechnology 21,484-490), (iv) dAb fragments consisting of VH or VL domains (Ward, ESet) al., Nature 341, 544-546 (1989), McCafferty et al., (1990) Nature, 348, 552-554, Holt et al. al.,(2003)Trends in Biotechnology 21,484 -490], (v) isolated CDR region, (vi) containing two linked Fab fragments The bivalent fragment F(ab')2 fragment, (vii) forms an antigen-binding site. A peptide linker enables the association of the two domains, VH domain and VL domain. A single-chain Fv molecule (scFv) in which nucleotides are linked (Bird et al., (1988)S science, 242, 423-426, Huston et al., (1988) P Examples include NAS USA, 85, 5879-5883). The present invention is Fab' Flag It also includes the ment. Furthermore, the two domains VL and VH of the Fv fragment are separate These are encoded by genes, but they are created by recombination, where the VL and VH regions are paired. The production of a single protein chain that forms a monovalent molecule (known as single-stranded Fv (scFv)). It can be linked using a synthetic linker that enables the production of such single-chain antibodies. This is intended to be encompassed by the term "compatible fragment". Specific embodiments of the present invention Therefore, the scFv molecule can be incorporated into the fusion protein. In some embodiments, The invention involves a single-stranded camelid antibody, (viii) a bispecific single-stranded Fv dimer (PCT / USA). (National Patent No. 92109965), and (ix) "Dye" constructed by gene fusion "Abody," polyvalent or multispecific fragment (International Publication No. 94 / 13804 pamphlet) Lett, Holliger, P. (1993) et al., Proc. Natl. Ac. (ad.Sci.USA 90 6444-6448) includes. The diamond body is VH and It is a bivalent bispecific antibody in which the VL domain is expressed on a single polypeptide chain, but the same chain Because a linker too short to match the two domains above is used, The pairing of the nucleotide with the complementary domain of the other chain is forced, forming two antigen-binding sites. For example, Holliger, P., et al. (1993) Proc. Natl. Ac ad.Sci.USA 90:6444-6448, Poljak, RJ, et a See l.(1994)Structure 2:1121-1123). The antibody-binding fragment is known in the art (Kontermann and Dubel eds.,Antibody Engineering(2001)Sp (ringer-Verlag. New York. 790 pp.). In several ways The present invention includes a single-domain antibody. Generally, the term "antibody" as used herein refers to an antibody. The term "antibody fragment" encompasses "antibody fragments." Antibody fragments are generally full-length It retains the antigen-binding properties of the antibody.

[0042] Fv, scFv, or diabody molecules are disulfides that link the VH and VL domains. It can be stabilized by incorporating a bridge (Reiter, Y. et al., Natu (re Biotech, 14, 1239-1245, 1996). Linked to the CH3 domain. Mini bodies including the scFv can also be manufactured (Hu, S. et al., (1996) (Cancer Res., 56, 3055-3061). Other examples of binding fragments. This is a carboxyl group of the heavy chain CH1 domain containing one or more cysteines from the antibody hinge region. The addition of a few residues at the terminal end results in Fab' and constant domain fragments that differ from Fab fragments. Fab' fragments in which the cysteine ​​residue of n supports a free thiol group are Fab'- It could be SH.

[0043] As used herein, "Fv" refers to a site that retains both antigen recognition and antigen binding sites. It can mean the smallest fragment of an antibody. As used herein, "Fab" means light This can mean an antibody fragment containing the constant domain of the chain and the CH1 domain of the heavy chain. The term "Ab" refers to a monoclonal antibody.

[0044] The "Fc region" or "Fc domain" is connected to the antibody receptor and complement C1q component on the cell. This refers to the polypeptide sequence that corresponds to or originates from the portion of the source antibody involved in binding. Fc is an antibody fragment that easily forms protein crystals, known as a "crystalline fragment." It is an abbreviation for "identifiable protein flags described by protein breakdown and digestion." Ment can define the overall general structure of immunoglobulin proteins. Originally, in the literature... As defined, the Fc fragment is a disulfide-linked heavy chain hinge region, CH2 and It consists of the CH3 domain. However, more recently, this term has come to mean CH3, CH2 and and a few hinges sufficient to form a disulfide linkage dimer with the second such chain This also applies to single strands consisting of only a portion. Review of the structure and function of immunoglobulins. Regarding this, see Putnam, The Plasma Proteins, Vol. V(A academic Press, Inc., 1987), pp.49-140 and Padl See an, Mol.Immunol.31:169-217, 1994. When used in detail, the term Fc includes naturally occurring sequence variants. In the embodiments, the antibodies or antibody fragments derived therefrom provided herein (e.g.) (Anti-ASC monoclonal antibody or its antibody fragment) has a modified Fc region or domain It has a modified Fc region or domain. In some cases, the modified Fc region or domain is the antibody obtained or due to it. It is possible to confer increased thermal stability to the resulting antibody fragment. Increased thermal stability This may result in an extended serum half-life. The Fc region or domain is subject to U.S. Patent No. 2016019 Modified as described in Specification No. 3295 (the contents of which are incorporated herein by reference). It is possible. As described in U.S. Patent No. 20160193295, the Fc area or The domain is characterized by the deletion of one or more cysteine ​​residues in the hinge region and one or more CH3 residues. It can be modified to have substitutions of sulfhydryl-containing residues in the tariff amino acids. In another embodiment, an antibody or antibody fragment derived therefrom provided herein The Fc region or of the (for example, anti-ASC monoclonal antibody or its antibody fragment) The main members are Wozniak-Knopp G, Stadlmann J, and Rukuer. F(2012)Stabilization of the Fc Fragment of Human IgG1 by Engineered Intradomain Disulfide Bonds.PLoS ONE7(1):e30083 (Contents) The domain has an intradomain disulfide bond as described in (which is incorporated herein by reference). The Fc region can be stabilized by engineering manipulation. In another embodiment Therefore, antibodies are incorporated herein by reference in International Publication No. 99 / 58572 (reference). It has an Fc region modified as described in (included). In yet another embodiment, Fc The territory or domain is as specified in U.S. Patent No. 9574010 (see this Specification for details). It can be modified as described in the text.

[0045] As used herein, the term "epitope" refers to immunoglobulin or immunoglobulin. It contains no protein determinants that have the ability to specifically bind to noglobulin fragments. Hmm. Epitopic determinants are usually chemically active surface groups of molecules such as amino acids and sugar side chains. It consists of a ring and usually has specific three-dimensional structural properties and specific charge properties. The term refers to the pair of immunoglobulin heavy chain variable (VH) region and light chain variable (VL) region. It also refers to the structural unit that binds in a more conventional manner. Epitopes are minimally binding to antibodies. Because it can specify the site, it becomes a target for antibody specificity.

[0046] "Apoptosis-related specs containing caspase-activating recruitment domains (CARDs)" The terms "protein-like protein" and "ASC" refer to the ASC gene or its isoform. Expression products or ASCs (e.g., NP_037390(Q9ULZ3-1) in humans) , NP_660183(Q9ULZ3-2) or Q9ULZ3-3 or in rats For NP_758825(BAC43754)), at least 65%, 75%, and 80% %, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the amino acid sequence This refers to proteins that share a common property and exhibit functional activity of ASC. "Activity" refers to any activity related to the physiological function of a protein. Function of ASC In terms of activity, for example, it is the activation of caspase-1 and the initiation of cell death by proteins. Mobilization is one example.

[0047] The terms "ASC gene" or "ASC nucleic acid" refer to the native ASC coding nucleic acid sequence. , ASC cDNA transcriptionable genome sequence and / or the above alleric variant and This term refers to mologs. This term encompasses double-stranded DNA, single-stranded DNA, and RNA.

[0048] As used herein, the term "inflammasome" or "canonical inflammasome" is used. The term "caspase-1" refers to a multiprotein that activates caspase-1 (e.g., at least 2 It means a complex of two proteins. Furthermore, the term "inflammasome" means a complex of two proteins. It activates Pase-1 activity, and consequently the processing of IL-1β, IL-18, and IL-33. This refers to a multi-protein complex that regulates activating and activating proteins. t al.2008, Li et al.2008 and Martinon et al. See 2002 (each of which is incorporated by reference). "NLRP "1 inflammasome", "NALP1 inflammasome", "NLRP2 inflammasome" "Mu", "NALP2 inflammasome", "NLRP3 inflammasome", "NALP "3-inflammasome", "NLRC4-inflammasome", "IPAF-inflammasome" The term "AIM2 inflammasome" or "AIM2 inflammasome" refers to at least caspase-1 and one This refers to a protein complex with an adapter protein, such as ASC. For example, "NL The terms "RP1 inflammasome" and "NALP1 inflammasome" are used by Casper Activation of Ze-1 and interleukin-1β, interleukin-18 and interleukin For the processing of Ikin-33, NLRP1, ASC, caspase-1, caspase This may refer to a multi-protein complex containing Ze-11, XIAP, and Panexin-1. The terms "NLRP2 inflammasome" and "NALP2 inflammasome" are: Mal containing NLRP2 (also known as NALP2), ASC, and caspase-1 This could mean a protein complex. On the other hand, "NLRP3 inflammasome" and "NAL The term "P3 inflammasome" refers to NLRP3 (also known as NALP3), A This can mean a multi-protein complex containing SC, and also "NLRC4 inflamma The terms "somal" and "IPAF inflammasome" are used in reference to NLRC4 (IPAF). It can also be said to mean a multiprotein complex containing ASC and caspase-1. In addition, the term "AIM2 inflammasome" is used for AIM2, ASC and Caspa. This could mean a multi-protein complex containing -se-1.

[0049] As used herein, the term "non-canonical inflammasome" means caspa Multiproteins that activate caspases other than -ase-1 (for example, at least two ta This refers to a complex of proteins. Noncanonical inflammasomes are complexes other than caspase-1. It can be composed of NLRs such as NLRP1 and NLRP3 that interact with caspases. However, the non-canonical NLRP1-caspase-8 inflammasome is NLRP-1, caspase It is composed of Pase-8 and ASC.

[0050] As used interchangeably in this specification, "amyloid precursor protein" and "APP" This refers to the expression product of the APP gene or isoform, the cleavage product of APP, or APP (for example) Acceptance numbers NP001129603.1, NP_001129601.1, P05067 ) at least 65%, 75%, 80%, 85%, 90%, 95%, 96%, 97% This can mean proteins that share 98% or 99% amino acid sequence identity. Non-limiting examples of cleavage products of PP (SEQ ID NO: 36) include soluble amyloid precursor proteins. Calcium α (sAPPα) (SEQ ID NO: 37), soluble amyloid precursor protein β (sAPPα) Pβ)(Sequence ID 38), Amyloid-β1-42(Aβ (1-42) )(Sequence No. 39) ) or amyloid-β1-40 (Aβ (1-40) )(Sequence No. 40) is an example.

[0051] As used interchangeably in this specification, "neurofilament light chain", "NfL", and "NFL" refers to the expression product of the NFL gene or isoform, the cleavage product of NFL, or At least 65% for NFL (e.g., acceptance number P07196) (sequence number 41), 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% This could mean proteins that share the same amino acid sequence.

[0052] As used herein, the term "control biomarker" or "control biomarker" is used in this specification. "Omarker proteins" are proteins that are associated with, indicate, or diagnose brain injury. Any gene or genetic material used in the compositions and methods of this disclosure, which are publicly known in the art, is used in this disclosure. This can mean the expression product or protein of a gene. For example, brain injury can be MCI and / or AD. It may also be a control biomarker or control biomarker tan The protein is amyloid-beta (Aβ), which is found in the NFL. (1-42) ), T-Tau, sAPPα or It could be sAPPβ. In some cases, the control biomarker for specific brain injury is These can be called control biomarkers for specific brain damage, such as MCI or A. The control biomarkers for D are, respectively, control MCI biomarkers or This could be called a control AD ​​biomarker.

[0053] As used herein, the term "sequence identity" refers to subunit matching. Align the two sequences to maximize their size, that is, taking gaps and insertions into account. When this happens, the same sub-segments at corresponding positions in two sequences (e.g., nucleic acid sequence, amino acid sequence) This refers to the percentage of units. Sequence identity is determined by sequence analysis software (for example, Sequence analysis software package from Accelrys CGC, San Diego, CA. It can be measured using (a device).

[0054] The terms "therapeutic effective dose" and "effective dosage" refer to the therapeutically (e.g., clinically) desired dose. It means a quantity sufficient to produce a result. The exact nature of the result depends on the nature of the disorder being treated. It will vary depending on the circumstances. For example, if the disorder being treated is SCI, the result will be This may include improvements in motor skills and locomotive function, and a reduction in spinal cord lesions. The composition can be administered at least once a day to at least once a week. However, it is not limited to the disease. Alternatively, the severity of the disability, past treatments, the subject's overall health and / or age, and any other pre-existing medical conditions. This includes specific factors such as the dosage and timing required to effectively treat the target. Those skilled in the art will understand that this can affect the g. Moreover, the therapeutically effective amount Treatment of a target with the composition of the present invention may consist of a single treatment or a series of treatments.

[0055] As used herein, the term “treatment” means a disease, a symptom of a disease, or a predisposition to a disease. For the purpose of curing, relieving, alleviating, reducing, modifying, treating, restoring, improving, or influencing a patient The application or administration of the therapeutic agent described herein is defined as or described herein. Identified by the method described, or from patients with the disease, symptoms of the disease, or predisposition to the disease. It is defined as the application or administration of a therapeutic agent to an isolated tissue or cell line.

[0056] The terms “patient,” “subject,” and “individual” are used interchangeably in this specification and refer to treatment. This refers to mammals that are subjected to treatment, such as human patients. In some cases, the method of the present invention is While not limited to these, rodents such as mice, rats, and hamsters, as well as It is used in the development of animal models for laboratory use, veterinary applications, and diseases, including primates. ru.

[0057] As used interchangeably in this specification, "Absent-in-Melanoma 2" and "AIM2" " is the expression product of the AIM2 gene or isoform or AIM2 (for example, acceptance number No. NX_014862, NP004824, XP016858337, XP005245 At least for 673, AAB81613, BAF84731, AAH10940) 65%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 9 This refers to proteins that share 9% amino acid sequence identity and exhibit functional activity of AIM2. obtain.

[0058] Where used interchangeably in this specification, "NALP1" and "NLRP1" refer to NALP 1 or the expression product of the NLRP1 gene or isoform or NALP1 (for example, Input number AAH51787, NP_001028225, NP_127500, NP_12 At least 65% and 75% for 7499, NP_127497, and NP055737. , 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% amino acids This refers to proteins that share sequence identity and exhibit NALP1 functional activity.

[0059] Where used interchangeably in this specification, "NALP2" and "NLRP2" refer to NALP 2 or the expression product of the NLRP2 gene or isoform or NALP2 (for example) Acceptance numbers NP_001167552, NP_001167553, NP_001167 At least 65%, 75%, 80%, 85% for 554 or NP_060322) %, 90%, 95%, 96%, 97%, 98%, or 99% amino acid sequence identity This refers to proteins that possess and exhibit NALP2 functional activity.

[0060] Where used interchangeably in this specification, "NALP3" and "NLRP3" refer to NALP 3 or the expression product of the NLRP3 gene or isoform or NALP3 (for example) Acceptance numbers NP_001073289, NP_001120933, NP_001120 934, NP_001230062, NP_004886, NP_899632, XP_ 011542350, XP_016855670, XP_016855671, XP_0 At least 65% and 75% of 16855672 or XP_016855673) %, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% amino acids This refers to proteins that share acid sequence identity and exhibit functional activity of NALP3.

[0061] Where used interchangeably in this specification, "NLRC4" and "IPAF" refer to NLRC4. Alternatively, an expression product of the IPAF gene or isoform or NLRC4 (for example, Input number NP_001186067, NP_001186068, NP_00128943 3 or NP_067032) at least 65%, 75%, 80%, 85%, Sharing 90%, 95%, 96%, 97%, 98%, or 99% amino acid sequence identity Furthermore, it refers to a protein that exhibits functional activity of NLRC4.

[0062] The terms "stroke" and "ischemic stroke" refer to a condition in which blood flow to a part of the brain or spinal cord is interrupted. It means when. The terms "ischemic stroke" and "transient ischemic stroke" refer to the brain or Blocking of arteries supplying oxygen-rich blood to the spinal cord restricts blood flow to the brain or part of the spinal cord. It means when interrupted. The term "hemorrhagic stroke" refers to a condition in which an artery in the brain or spinal cord leaks blood. This refers to a situation where blood flow to part of the brain or spinal cord is interrupted due to a rupture or burst.

[0063] "Traumatic injury to the CNS" can result in permanent or temporary impairment of CNS function. This refers to any injury to the CNS caused by a certain mechanical force.

[0064] As used herein, the term “inflammatory aging” refers to the processes that may occur as an organism ages. This can mean chronic low-grade inflammation. Inflammatory aging is macrophage-centered and affects the gastrointestinal tract. Several tissues and organs, including the microbiome, are involved, and there is a conflict between pro-inflammatory and anti-inflammatory responses. It can be characterized by a complex balance between the two. In some cases, inflammatory aging is chronic inflammation. This may indicate a disease-promoting state. The main inflammatory stimuli that can be used to characterize or associate inflammation are: Derived from damaged and / or dead cells and organelles (cellular debris), they become receptors of the innate immune system. They may be represented by more recognizable endogenous / self, misconfigured, or modified molecules. Their production is It is physiological and increases with age, but is mediated through autophagy and / or mitophagy. The disposal of these by the proteasome gradually decreases. This "autoreactivity / autoimmune The process can accelerate and propagate the aging process locally and systemically, leading to the onset of chronic diseases. It can amplify the progression.

[0065] Methods involving conventional molecular biology techniques are described herein. Such techniques are described herein. It is widely known in the field of surgery, Molecular Cloning: A Laboratory ory Manual,3rd ed.,vol.1-3,ed.Sambrooke t al.,Cold Spring Harbor Laboratory Pres. s, Cold Spring Harbor, NY, 2001 and Current Protocols in Molecular Biology, ed.Ausube l et al., Greene Publishing and Wiley-Int. This is described in detail in methodological textbooks such as erscience, New York, 1992. (This is updated regularly.) Immunological techniques are widely known in this field, and Adv ances in Immunology, volume 93, ed.Frederi ck W. Alt, Academic Press, Burlington, MA, 20 07;Making and Using Antibodies:A Practical al Handbook, eds. Gary C. Howard and Matthe w R. Kaser, CRC Press, Boca Raton, FL, 2006, M edical Immunology,6th ed.,edited by Gabr iel Virella,Informa Healthcare Press,Lon don, England, 2007 and Harlow and Lane ANTIBO DIES:A Laboratory Manual,Cold Spring Har bor Laboratory Press,Cold Spring Harbor, This is described in detail in methodological textbooks such as NY, 1988.

[0066] exterior This specification includes information on diseases, disorders, or conditions that are caused by or related to inflammation. Compositions and methods for evaluating or diagnosing suspected patients are provided. This method is for patients Level of at least one inflammasome protein in biological samples obtained from Measuring inflammation and related diseases, disorders, or conditions caused by or associated with inflammation. The purpose is to determine the presence or absence of a related protein signature, and the protein signature The net contains elevated levels of at least one inflammasome protein, It is important to determine if the patient exhibits the presence of a protein signature, and if inflammation or inflammation is present. This may include selecting patients based on whether they have a related disease, disorder, or condition. In some cases, this method involves at least one control biomarker protein. Further including measuring the quality expression level, the protein signature indicates elevated expression. Further includes at least one control biomarker protein at a low level. In both cases, the expression level of one type of control biomarker protein indicates inflammation or inflammation. It has been previously indicated that the cause or related disease, disorder, or condition is related to It is one of the proteins. Inflammation can be congenital immunoinflammatory. Inflammation is related to the inflammasome. It may be a inflammatory condition. Diseases, disorders, or pathologies include brain injury, age-related diseases, inflammatory aging, and autoimmune diseases. The group can be selected from sexual, autoinflammatory, metabolic, or neurodegenerative diseases. The disease, disorder, or condition is inflammatory aging. In some cases, age-related diseases include age-related macular degeneration. It is degenerative brain disease (AMD). In some cases, the disease, disorder, or condition is brain injury. Brain injury is The group can be selected from the following categories: traumatic brain injury (TBI), stroke, and spinal cord injury (SCI). Autoimmune or neurodegenerative diseases include amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. (AD), Parkinson's disease (PD), muscular dystrophy (MD), immunodeficiency muscle CNS Debilitation, systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, inflammatory bowel disease (e.g., crow). The following can be selected: ulcerative colitis and multiple sclerosis (MS). Metabolic diseases are, Metabolic syndrome, obesity, diabetes, diabetic nephropathy or diabetic kidney disease (DKD), insulin Phosphorus resistance, atherosclerosis, lipid storage disorders, glycogen storage disorders, medium-chain acyl cofermentation Dehydrogenase A deficiency, non-alcoholic fatty liver disease (e.g., non-alcoholic fatty liver disease) The options are NASH (non-alcoholic steatohepatitis) and gout. Autoinflammatory diseases are associated with cryopyrin therapy. It may be a period syndrome (CAPS). CAPS is a familial cold autoinflammatory syndrome (FCA). S), Mackle-Wells syndrome (MWS) and neonatal-onset multiorgan inflammatory disease (NO It can include MID. In one embodiment, brain injury is MS. In another embodiment, In one embodiment, the brain injury is a stroke. In yet another embodiment, the brain injury is a TBI. In yet another embodiment, the brain injury is MCI. This is AD. In embodiments where the brain injury is MCI or AD, a control biomarker - The protein is NFL, amyloid-β (Aβ (1-42) ), T-Tau, sAPP It may be α, sAPPβ, or any combination thereof. The disease, disorder, or condition is inflammation. It may be age-related aging or age-related disease. In another embodiment, the age-related disease is age-related macular degeneration ( It is AMD.

[0067] Furthermore, this specification includes information regarding diseases, disorders, or conditions caused by or related to inflammation. Methods for treating patients who are affected or suspected of being affected are also provided. Inflammation is congenital. It may be sexual immunological inflammation. The inflammation may be inflammasome-associated inflammation. Disease, disorder or illness The conditions include brain injury, age-related diseases, inflammatory aging, autoimmune conditions, autoinflammatory conditions, metabolic conditions, or neurodegeneration. A group of diseases can be selected. In some cases, the disease, disorder, or condition is inflammatory aging. In some cases, the age-related disease is age-related macular degeneration (AMD). The disease, disorder, or condition is brain injury. Brain injury includes traumatic brain injury (TBI), stroke, and The group can be selected from those with spinal cord injury (SCI). Autoimmune or neurodegenerative diseases are Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Muscular dystrophy (MD), immune dysfunction muscle CNS weakness, systemic lupus erythematosus, lupus kidney Inflammation, rheumatoid arthritis, inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis), and multiple cirrhosis It is possible to select from metabolic syndrome (MS). Metabolic diseases include metabolic syndrome, obesity, diabetes, Diabetic nephropathy or diabetic kidney disease (DKD), insulin resistance, atherosclerosis, lipids Storage disorders, glycogen storage disorders, medium-chain acyl coenzyme A dehydrogenase deficiency, non-alcoholic You can choose from alcoholic fatty liver disease (e.g., non-alcoholic steatohepatitis (NASH)) and gout. It is possible. Autoinflammatory diseases can be cryopyrin-associated periodic syndromes (CAPS). CAPS is the familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (M This specification may include WS) and neonatal-onset multiorgan inflammatory diseases (NOMID). Any treatment method provided is for those suffering from an inflammation-related disease, disorder, or condition. It may be necessary to administer treatment to patients suspected of having the disease. Provided herein By treating inflammation-related diseases, disorders, or conditions in such a manner, It is possible to reduce inflammation in patients. Reduction is possible in the control group (e.g., untreated). This may be compared to patients with the treatment and / or patients before the treatment. In some cases, the treatment is a standard treatment. It is a quasi-therapeutic procedure. In some cases, the procedure is a neuroprotective procedure. Protective measures may include agents that reduce excitotoxicity, oxidative stress, and inflammation. Therefore, Preferred neuroprotective treatments include, but are not limited to, methylprednisolone, 17 Alpha-estradiol, 17-beta-estradiol, ginsenoside, progesterone Steroids, simvastatin, deprenyl, minocycline, resveratrol and other steroids Lutamate receptor antagonists (e.g., NMDA receptor antagonists) and acid-fast receptor antagonists Contains a activating agent. In some embodiments, the treatment is directed toward inflammasome proteins. Antibodies or their binding fragments, such as the inframaso provided herein. These are antibodies that target mucoproteins.

[0068] Furthermore, this specification includes apoptosis-related domains containing caspase-activating recruitment domains. Monoclonal antibodies that specifically bind to Peck-like protein (ASC) or antibody flash films thereof The ligation is also provided. Monoclonal antibodies or their fragments are KKFKLKLL Contains or consists of the amino acid sequence of SVPLREGYGRIPR (SEQ ID NO: 5) It can specifically bind to the antigenic fragment of ASC that is essentially derived from it. In this embodiment, the present invention relates to a method for treating inflammation in a subject, monoclonal The use of antibodies or antibody fragments thereof is intended. Inflammation is a disease, disorder, or inflammation-related condition. This can be caused by patients suffering from a disease. The inflammation may be congenital immunoinflammatory. The inflammation may be inflammasome-associated inflammation. The disease, disorder, or condition may be brain injury, age-related disease. Select from the group consisting of disease, inflammatory aging, autoimmune, autoinflammatory, metabolic, or neurodegenerative diseases. It is possible. In some cases, the disease, disorder, or condition is inflammatory aging. Age-related diseases include age-related macular degeneration (AMD). In some cases, the term refers to a disease, disorder, or condition. This is a brain injury. Brain injuries include traumatic brain injury (TBI), stroke, and spinal cord injury (SCI). A selection is possible from the following groups. Autoimmune or neurodegenerative diseases include amyotrophic lateral sclerosis (A). LS, Alzheimer's disease (AD), Parkinson's disease (PD), Muscular dystrophy (MD) ), immune dysfunction muscle CNS weakness, systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, inflammation You can choose from genital bowel diseases (e.g., Crohn's disease and ulcerative colitis) and multiple sclerosis (MS). Metabolic diseases include metabolic syndrome, obesity, diabetes, diabetic nephropathy, or diabetes. Kidney disease (DKD), insulin resistance, atherosclerosis, lipid storage disorders, glycogen Storage disease, medium-chain acyl coenzyme A dehydrogenase deficiency, non-alcoholic fatty liver disease (for example) For example, non-alcoholic steatohepatitis (NASH) and gout can be selected. Autoinflammatory disease The patient may have cryopyrin-associated periodic syndrome (CAPS). CAPS is a familial influenza. Autoinflammatory syndrome (FCAS), Mackle-Wells syndrome (MWS), and neonatal onset It can encompass multi-organ inflammatory diseases (NOMIDs). One embodiment is provided herein. The monoclonal antibody or its antibody fragment is subject to the U.S. Law 8,685,400 As described in the specification (the contents of which are incorporated herein by reference in their entirety) It can be used in a method to reduce inflammation in dairy animals. Monoclonal anti The body or its antibody fragments are, for example, compositions such as the pharmaceutical compositions provided herein. It can exist within. In some cases, monoclonal antibodies or their fragments are present in this It is used in combination with one or more other agents in the treatment method provided in the specification. The agent is any of the activators provided herein (e.g., EV uptake inhibitors) and / or Other inflammasome components (e.g., IL-18, caspase-1, NALP1, AIM) It may be an antibody or antibody fragment against (2, etc.).

[0069] Diagnostic methods In some cases, this specification refers to diseases, disorders, or other conditions caused by or related to inflammation. or at least 1 in a biological sample obtained from a patient suspected of having the disease To detect the expression levels of inflammasome proteins in a species and control biological To detect the expression level of at least one control protein in the sample, Suspected of having inflammation or a disease, disorder, or condition caused by or related to inflammation At least one inflammasome protein in a biological sample obtained from a patient Expression levels of at least control proteins in control biological samples To compare with the current level, and based on that comparison, to identify inflammation or diseases caused by or related to inflammation. This may include selecting patients for having a disorder or condition, or for inflammation or inflammation-related conditions. Or a person who diagnoses or evaluates patients suspected of having related diseases, disorders, or conditions. The law is provided. In some cases, at least one type in the control biological sample Compared to the expression levels of control proteins, inflammation or inflammation-induced or related levels In biological samples obtained from patients suspected of having a disease, disorder, or condition Increased expression levels of at least one inflammasome protein Depending on the level, it may indicate inflammation or a disease, disorder, or condition caused by or related to inflammation. Patients are selected. In some cases, at least in the control biological sample Compared to the expression level of one control protein, inflammation or inflammation-related or related Biological samples obtained from patients suspected of having related diseases, disorders, or conditions. The detected decrease in the expression level of at least one inflammasome protein during the pull Depending on the level of expression, inflammation or diseases, disorders, or conditions caused by or related to inflammation may be diagnosed. Patients are selected as having the condition. In some cases, control biological samples are used. Patients who are not suspected of having a disease, disorder, or condition caused by or related to a disease or inflammation It may be a biological sample obtained from the subject, as well as at least one control. Proteins are involved in inflammation or diseases, disorders, or conditions caused by or related to inflammation. At least one type of insect detected in biological samples obtained from patients suspected of having the disease. It may be a flammosome protein. In some cases, control biological samples are , suspected of having inflammation or a disease, disorder, or condition caused by or related to inflammation It may be a biological sample obtained from a patient, and at least one control The control protein can be a control biomarker protein. Omarker proteins are those whose expression levels indicate inflammation or a disease caused by or related to inflammation. It could be any protein that has been previously shown to be associated with a disorder or pathological condition. In one embodiment, the elevated expression level of the control biomarker protein is associated with flame Diseases, disorders, or conditions related to or diagnosed as resulting from or associated with inflammation It has been shown in advance that in one embodiment, a disease, disorder or The pathological condition is MCI or AD, and at least one control protein is NF L, amyloid-β (Aβ) (1-42) ), T-Tau, sAPPα and sAPPβ A selected control biomarker protein. In one embodiment, it is caused by inflammation. The associated disease, disorder, or condition is NASH, and at least one control The protein is selected from Gal-3 and CRP (hs-CRP) as a control protein. It is an omarker protein. In one embodiment, in a biological sample obtained from a patient By measuring the expression level of at least one inflammasome protein, inflammation can be detected. In patients suspected of having a disease, disorder, or condition caused by or related to the above, inflammation Persons provided herein for the purpose of evaluating or diagnosing a disease, disorder, or condition that is the cause or related to the disease, disorder, or condition. In all cases, the modified expression levels are related to diseases, disorders, or conditions caused by or associated with inflammation. In combination with determining the expression levels of biomarkers that are known or suspected to be related. It is feasible. In one embodiment, at least one of the biological samples obtained from the patient By measuring the expression levels of inflammasome proteins in a species, it is possible to determine whether inflammation is caused by or related to inflammation. In patients suspected of having a related disease, disorder, or condition, inflammation is the cause or related Any method provided herein for evaluating or diagnosing a disease, disorder, or condition is This can be performed in combination with one or more additional diagnostic assessments. Biological samples obtained from patients Detecting modified expression levels of at least inflammasome proteins in the sample is 1 A specific disease or disorder caused by or related to inflammation, as determined using one or more additional diagnostic assessments. It can be used to confirm the diagnosis of a disease state. In biological samples obtained from patients At least the detection of altered expression levels of inflammasome proteins is one or more steps The determination of specific diseases, disorders, or conditions caused by or related to inflammation using the diagnostic assessment. It can be used to increase the degree or to enhance the diagnosis. One or more additional Diagnostic evaluation includes assessment of clinical parameters, examination of morphological indicators in tissue biopsy, and From the evaluation or assessment of symptoms related to specific diseases, disorders, or conditions caused by or associated with inflammation. It is possible to select from the following groups. Inflammasome tannins in biological samples obtained from patients Any diagnostic methods provided herein in relation to determining the level of protein are caused by inflammation. Alternatively, it can be used as an adjunct to known diagnostic methods for specific related diseases, disorders, or conditions.

[0070] In other words, in this specification, inflammation or a disease, disorder, or illness caused by or related to inflammation At least one type of i found in biological samples obtained from patients suspected of having the disease Inframasome proteins and at least one control biomarker protein To detect the expression level of at least one of the i in the control biological sample. Inframasome proteins and at least one control biomarker protein To detect the expression level of and to identify inflammation or diseases or disorders caused by or related to inflammation. at least one of the biological samples obtained from a patient suspected of having the disease. inflammasome proteins and at least one control biomarker protein This involves comparing the expression level of the substance with that of a control biological sample, and based on that comparison... Patients are diagnosed with inflammation or a disease, disorder, or condition caused by or related to inflammation. A disease, disorder, or illness that may include the selection of inflammation or a disease caused by or related to inflammation. A method is provided for diagnosing or evaluating patients suspected of having the condition. In some cases, Compared to the expression levels in the troll biological sample, inflammation or inflammation-induced or related Biological samples obtained from patients suspected of having the disease, disorder, or condition described above. At least one inflammasome protein and at least one control protein in the brilliance The increased expression level of the detected biomarker protein indicates inflammation or Patients are selected if they have a disease, disorder, or condition caused by or related to inflammation. In some cases, compared to the expression levels in a control biological sample, inflammation or From patients suspected of having a disease, disorder, or condition caused by or related to inflammation At least one inflammasome protein and at least In both cases, the detected expression levels of one type of control biomarker protein were reduced. At the current level, the patient has a disease, disorder, or condition caused by or related to inflammation. Patients are selected as such. In some cases, control biological samples are inflammatory or Is the subject not suspected of having a disease, disorder, or condition caused by or related to inflammation? It may be a biological sample obtained from, and at least one control protein The patient is suspected of having inflammation or a disease, disorder, or condition caused by or related to inflammation. At least one type of inflamma detected in biological samples obtained from patients with the condition It may be a somal protein. The control biomarker protein is its expression level The fact that the lu is related to inflammation or diseases, disorders, or conditions caused by or associated with inflammation is a prior matter. It may be any of the proteins shown. In one embodiment, control bio Elevated expression levels of marker proteins indicate inflammation or inflammation-related diseases. It has been indicated in advance that it is related to or will lead to the diagnosis of a disorder or condition. In this context, diseases, disorders, or conditions caused by or related to inflammation are MCI or AD, and less At the very least, one type of control protein is NFL, amyloid-β (Aβ). (1-42) ), a control biomarker selected from T-Tau, sAPPα, and sAPPβ It is a protein. In one embodiment, a disease, disorder, or condition caused by or related to inflammation is NA It is SH, and at least one control protein is Gal-3 and CRP( This is a control biomarker protein selected from hs-CRP.

[0071] In one embodiment, this specification includes at least one biological sample obtained from a patient. Measuring the levels of inflammasome proteins in a species and proteins associated with MS Determining the presence or absence of a signature, the protein signature is elevated. To determine that it contains at least one inflammasome protein at a certain level, and the patient If a patient exhibits the presence of a protein signature, they may be selected as having MS. A method for diagnosing or evaluating patients with multiple sclerosis (MS), including [specific example], is provided. The patient may present clinical symptoms consistent with MS. Through this method, the patient can be diagnosed with any type of MS known in the art. S stands for relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PMS). This may be PMS (post-inflammatory syndrome) or progressive recurrent MS (PRMS). In some cases, this method may be modified. Control biomarkers whose expressed levels have been shown to be associated with MS, for example. For example, measuring the expression levels of NFL, etc., in samples obtained from patients, and in patients To reliably diagnose MS, one or more modified inflammasome proteins are used. Modified expression level of the control biomarker in combination with current level of detection This further includes using detection. In some cases, this method is used in patients in association with MS. To evaluate clinical features / symptoms and to reliably diagnose MS in patients, Modified expression levels of one or more inflammasome proteins in the obtained samples This further includes using detection.

[0072] In another embodiment, this specification describes how to diagnose or treat a patient suspected of having a stroke. A method for evaluation is provided, and this method is used to evaluate at least one of the biological samples obtained from the patient. Measuring the level of one type of inflammasome protein and stroke or stroke-related injury Determining the presence or absence of a protein signature associated with harm, The quality signature contains elevated levels of at least one inflammasome protein. Hmm, to make a decision, if the patient exhibits the presence of a protein signature, then the patient will suffer a stroke. This includes selecting patients as having the condition described above. Patients are publicly available in the art that matches the description of stroke. It may present with any of the following clinical symptoms. Stroke can be ischemic stroke, transient ischemic stroke, or It may be a hemorrhagic stroke. In some cases, this method is used when the modified expression level is associated with stroke. The expression levels of control biomarkers that have been shown to be related can be obtained from patients. To measure in the sample and to reliably diagnose stroke in the patient, one or more The control is performed in combination with the detection of modified expression levels of inflammasome proteins. This further includes using the detection of modified expression levels of biomarkers. In that case, this method evaluates the patient's clinical characteristics / symptoms in relation to stroke, and the patient In order to reliably diagnose stroke, one or more influenza cells are found in the sample obtained from the patient. This further includes using the detection of modified expression levels of ramasomal proteins.

[0073] In one embodiment, this specification includes at least one biological sample obtained from a patient. Measuring the levels of inflammasome proteins in a species and proteins associated with TBI The purpose is to determine the presence or absence of a protein signature, where the protein signature is superior To determine that it includes at least one inflammasome protein at elevated levels, If a patient presents with a protein signature, select the patient as having TBI. A method for diagnosing or evaluating patients with traumatic brain injury (TBI) is provided, which includes the following: The patient may present clinical symptoms consistent with TBI. The methods and combinations provided herein Through the use of the product, patients can be diagnosed with any type of TBI known in the art. In some cases, this method has shown that the modified expression levels are associated with TBI. The expression levels of the control biomarkers were measured in samples obtained from patients. To determine and to reliably diagnose TBI in patients, one or more inflammasomes The control biomarker is identified in combination with the detection of the modified expression level of the protein. This method further includes using the detection of modified expression levels. In some cases, this method This involves evaluating the patient's clinical characteristics / symptoms in relation to TBI, and assessing TBI in patients. To ensure accurate diagnosis, one or more inflammasome proteins are present in the sample obtained from the patient. This further includes using the detection of modified expression levels of the substance.

[0074] In one embodiment, this specification provides a method for diagnosing or evaluating a patient with cognitive impairment. Cognitive impairment can be mild or severe. In one embodiment, cognitive impairment is mild cognitive impairment. This is a mild cognitive impairment (MCI). This method involves at least one of the biological samples obtained from the patient. Measuring the levels of inflammasome proteins in a species and cognitive impairment (e.g., MCI) To determine the presence or absence of a protein signature related to ) The quality signature contains elevated levels of at least one inflammasome protein. Hmm, to make a decision, and if the patient exhibits the presence of a protein signature, cognitive impairment (e.g.) For example, this includes selecting patients who have MCI (Mild Cognitive Impairment). In some cases, this method , to measure the expression level of at least one control biomarker protein. Furthermore, the protein signature is elevated in expression levels of at least one of the following compounds. Further contains troll biomarker proteins. At least one control bio The marker protein has been previously shown to have expression levels associated with brain injury. That protein. At least one control biomarker protein is N FL, amyloid-β (Aβ) (1-42) ), T-Tau, sAPPα or sAPPβ The following options are available. The patient may present clinical symptoms consistent with cognitive impairment (e.g., MCI). Through the use of the methods and compositions provided herein, patients may experience conditions known in the art. It is possible to diagnose one of the types of cognitive impairment, such as MCI. The patient has MCI. Examples of symptoms that the subject often exhibits include amnesia (more frequent forgetfulness and / or forgetfulness of important events). Forgetfulness, lack of concentration (loss of flow of thought), when making decisions, understanding instructions, or planning things. This may include feelings of anxiety or confusion, difficulty moving in unfamiliar environments, and / or impulsivity and unsure judgment. Individuals with MCI may also experience depression, irritability, anxiety, or apathy. In some cases, The method involves a control group in which modified expression levels have been shown to be associated with MCI. Omarkers, for example, the NFL, amyloid-beta (Aβ) (1-42) ), T-Tau, sAP The expression levels of Pα, sAPPβ, etc. are measured in samples obtained from patients, and Modification of one or more inflammasome proteins to reliably diagnose MCI in individuals Modified expression of the control biomarker in combination with detection of the expression level This further includes using level detection. In some cases, this method is related to MCI. To evaluate the patient's clinical characteristics / symptoms in a series of steps, and to reliably diagnose MCI in the patient. Therefore, one or more modified inflammasome proteins in samples obtained from patients This further includes using the detection of expression levels.

[0075] In one embodiment, this specification describes a method for diagnosing or evaluating patients with Alzheimer's disease (AD). A law is provided. In some embodiments, Alzheimer's disease causes dementia. In some embodiments, the patient is in the early stage (mild), middle stage (moderate), or late stage Has AD classified as (severe) stage. In one embodiment, AD is in the early stage There is. In some embodiments, AD is in the middle stage. In some embodiments, AD is in the late stage. The method measures the expression level of at least one inflammasome protein in a biological sample obtained from a patient, and determines the presence or absence of a protein signature related to cognitive impairment (e.g., , AD), wherein the protein signature includes at least one inflammasome protein at an elevated level, determining, and selecting the patient as having cognitive impairment (e.g., AD) if the patient exhibits the presence of the protein signature. In some cases, the method further includes measuring the expression level of at least one control biomarker protein, and the protein signature further includes at least one control biomarker protein at an elevated expression level. The at least one control biomarker protein is any protein whose expression level has been previously shown to be related to brain injury. The at least one control biomarker protein is selected from NFL, amyloid-β (Aβ ), T-Tau, sAPPα or sAPP β. The patient may exhibit clinical symptoms consistent with AD. Through the use of the methods and compositions provided herein, a patient can be diagnosed with any type of A D known in the art, such as mild stage, moderate stage, late stage, etc. Examples of symptoms commonly presented by subjects suffering from AD include amnesia (more frequent forgetting and / or forgetting of important events), lack of concentration (loss of train of thought), during decision-making, when understanding instructions, or when performing tasks that require sustained attention and quick thinking, such as shopping, handling finances, driving, cooking, etc. (1-42) ), T-Tau, sAPPα or sAPP β. The patient may exhibit clinical symptoms consistent with AD. Through the use of the methods and compositions provided herein, a patient can be diagnosed with any type of A D known in the art, such as mild stage, moderate stage, late stage, etc. A subject suffering from AD can be diagnosed with any type of AD known in the art, such as mild stage, moderate stage, late stage, etc. Examples of symptoms commonly presented by subjects suffering from AD include amnesia (more frequent forgetting and / or forgetting of important events), lack of concentration (loss of train of thought), during decision-making, when understanding instructions, or when performing tasks that require sustained attention and quick thinking, such as shopping, handling finances, driving, cooking, etc. or when performing tasks that require sustained attention and quick thinking, such as shopping, handling finances, driving, cooking, etc. This includes feelings of anxiety or confusion when planning things, difficulty moving in unfamiliar environments, difficulty carrying out tasks, and reading. Immediately following this, there is an increasing risk of forgetting documents, losing or misplacing valuable items, and experiencing difficulties in planning or organizing. Addition, confusion, difficulty controlling bladder or bowel movements, changes in personality and behavior, sleep patterns Changes in [unclear], communication difficulties, vulnerability to infection, and / or impulsive and suspicious judgments are among the factors that may be contributing to this. It is possible. Individuals with AD may also experience depression, irritability, anxiety, or apathy. In some cases, This method is a control group in which modified expression levels have been shown to be associated with AD. Omarkers, for example, the NFL, amyloid-beta (Aβ) (1-42) ), T-Tau, sAP The expression levels of Pα, sAPPβ, etc. are measured in samples obtained from patients, and To reliably diagnose AD in individuals, one or more inflammasome proteins are modified. The modified expression level of the control biomarker is detected in combination with the detection of the specified expression level. This further includes using bell detection. In some cases, this method is in relation to AD. To evaluate the patient's clinical characteristics / symptoms and to reliably diagnose AD in the patient Modified expression levels of one or more inflammasome proteins in samples obtained from individuals This further includes using bell detection.

[0076] In one embodiment, this specification describes how to diagnose or evaluate patients with age-related inflammation or inflammatory aging. A method is provided. This method involves at least one of the biological samples obtained from a patient Measuring the expression levels of inflammasome proteins and the tanning of inflammatory aging The purpose is to determine the presence or absence of a protein signature, and the protein signature is This includes the elevated levels of at least one type of inflammasome protein, which can be determined. If a patient exhibits the presence of a protein signature, the patient is considered to have inflammatory aging. This includes selecting a control bar. In some cases, this method includes at least one control bar. This further includes measuring the expression level of iomarker proteins and protein signature The indicator is at least one control biomarker protein with elevated expression levels. It further includes at least one control biomarker protein, at an expression level It is one of the proteins that has been previously shown to be associated with inflammatory aging. It may present with clinical symptoms consistent with inflammatory aging.

[0077] In one embodiment, this specification describes a method for diagnosing or evaluating patients with age-related macular degeneration (AMD). A method is provided. In some embodiments, AMD patients have a damaged macula. The macula is the retina. It is part of the following. In some embodiments, AMD patients undergo central vision and fine vision loss. It allows you to test while maintaining peripheral vision. AMD has two types: Dry AMD and Wet AMD. AMD exists. Dry AMD is characterized by insoluble extracellular aggregates or drusen in the macula. It is characterized by the presence of . Drusen is found in the retinal pigment epithelium (RPE) and photoreceptor layer. It can have an impact and, as it progresses, eventually lead to RPE atrophy and severe vision loss. A rare AMD. The morphology is wet AMD characterized by choroidal angiogenesis (CNV), and is untreated. If left untreated, it can rapidly progress to blindness. In some embodiments, the method described herein This is used to diagnose wet AMD patients. In some embodiments, this specification The method described is used to diagnose patients with dry AMD. In some embodiments, The methods described herein are used to diagnose wet AMD and dry AMD. In some embodiments, the methods described herein are used for wet AMD and dry AMD. It is used to differentiate patients with MD. Such differentiation is effective for wet AMD. Treatments such as anti-vascular endothelial growth factor (anti-VEGF) therapy are not effective for dry AMD. This is important for this purpose. This method involves at least one of the biological samples obtained from the patient. Measuring the expression levels of inflammasome proteins and proteins related to AMD The purpose is to determine the presence or absence of a protein signature, where the protein signature is To determine that it includes elevated levels of at least one type of inflammasome protein. If a patient presents with a protein signature, select the patient as having AMD. This includes doing so. In some cases, this method includes at least one control biomass. Further including measuring the expression level of the maker protein, the protein signature is Furthermore, the elevated expression levels of at least one control biomarker protein It includes at least one control biomarker protein whose expression level is AM It is one of the proteins that has been previously shown to be associated with D. The patient has AMD. The patient may present with consistent clinical symptoms. The patient may exhibit abnormal changes in the macular region, such as macular optical coherence. As revealed by comprehensive eye examinations including optical coherence tomography (OCT), the macula The presence of drusen or fluid may result in pigment epithelial exfoliation. The methods and Through the use of the composition, the patient can have any type of AMD known in the art, for example It can be diagnosed as either wet AMD or dry AMD. The symptoms presented in subjects with AMD. Common symptoms include blurred or unclear vision, and straight lines in text on a page appearing wavy. Or it may appear distorted, blurred areas on the printed page, or when reading details in low light. This may manifest as difficulty seeing, extra perception of bright, dark, or blurred areas, or as appearing in the visual center. This may include whiteout or altered color perception. In some cases, this method may be modified. Expression levels of control biomarkers that have been shown to be associated with AMD Measuring Bell in patient samples and reliably diagnosing AMD in patients To do this, combine the detection of modified expression levels of one or more inflammasome proteins. In conjunction with this, detection of the modified expression levels of the aforementioned control biomarkers is used. This further includes: In some cases, this method can assess the clinical characteristics / symptoms of patients in relation to AMD. To evaluate and to obtain samples from patients in order to reliably diagnose AMD in patients This involves using the detection of modified expression levels of one or more inflammasome proteins. It also includes toto.

[0078] In one embodiment, this specification describes the diagnosis of patients with non-alcoholic fatty liver disease (NAFLD). A method for evaluating or assessing is provided. This method involves a small amount of biological samples obtained from patients. At least one type of inflammasome protein expression level is measured, and NAFLD To determine the presence or absence of the relevant protein signature, the protein signature The signature contains elevated levels of at least one inflammasome protein. To determine if the patient has NAFLD, if the patient exhibits the presence of a protein signature. This includes selecting patients as such. In some cases, this method involves at least one type of This further includes measuring the expression level of control biomarker proteins, and proteins The crystalline signature is a control biomarker with elevated expression levels of at least one control biomarker. - Further contains proteins. At least one control biomarker protein is included. , any of the proteins whose expression levels have been previously shown to be associated with NAFLD Yes. Patients may present clinical symptoms consistent with NAFLD. The methods and Through the use of the composition, the patient may have any type of NAFLD known in the art. For example, it can be used to diagnose fatty liver or non-alcoholic steatohepatitis (NASH).

[0079] In one embodiment, it is shown herein that the modified expression level is associated with NASH. In combination with determining the expression levels of biomarkers present or suspected of being present, NASH At least one of the biological samples obtained from patients who are suffering from or suspected of having the disease By measuring the expression level of one type of inflammasome protein, it is possible to determine if a person suffers from NASH. A method for diagnosing or evaluating patients suspected of having the disease is provided. In one embodiment, the present invention The detailed report includes, in combination with one or more additional diagnostic evaluations, suspected cases of NASH. At least one inflammasome protein in a biological sample obtained from a patient By measuring the expression level, patients suspected of having NASH can be diagnosed or evaluated. A method is provided that evaluates the amount of at least the inframa in the biological sample obtained from the patient. Detection of altered expression levels of somal proteins is performed using one or more additional diagnostic assessments. It can be used to confirm the determined NASH diagnosis. Biological samples obtained from the patient Detecting modified expression levels of at least inflammasome proteins in the sample is 1 To increase the certainty of the determination made using one or more additional diagnostic assessments or to improve the NASH diagnosis It can be used to enhance the assessment of clinical parameters. One or more additional diagnostic assessments can be used to evaluate clinical parameters. , examination of morphological indicators in liver biopsy, levels of inflammatory cytokines and chemokines Determination of liver function, evaluation of adipokines, evaluation of liver fibrosis biomarkers, evaluation of oxidative stress A group consisting of the evaluation of mitochondrial dysfunction and the evaluation of apoptotic biomarkers. These are selectable. Inflammatory cytokines used as biomarkers for NASH and Examples of chemokines include TNF-alpha, IL-6, and chemokine CC-chemokine. Gand-2 (chemoattractant protein-1) and highly sensitive C-reactive protein (hs-CRP) Examples of apoptosis biomarkers include CK-18, sFas, and Hyaluronic acid is one example. Examples of adipokines include leptin and adiponectin. Examples include resistin, retinol-binding protein 4, and ghrelin. Oxidative stress Examples of biomarkers include 13-hydroxyoctadecadienoic acid, SOD2, and cytophosphate. Chromium p450 2E1 (CYP2E1) is one example. Mitochondrial dysfunction bio Examples of markers include CK-7 and CK-18. These are used as liver fibrosis markers. It contains galectin-3 (Gal-3), hyaluronic acid, and procollagen III N-terminal peptide. Examples include Tydo, TGF-β, and TIMP1. Examples of clinical parameters include body weight index. Waist circumference, blood or serum levels of alanine aminotransferase (ALT), asparagus Ginate aminotransferase (AST), total cholesterol, low-density lipoprotein Quality, triglycerides, glucose, insulin resistance, and metabolism and proteomic proteins This can be selected from file analysis.

[0080] In one aspect of the present invention, inflammation or inflammation-related diseases, disorders, or conditions (e.g., NA) Suspected of having SH, MCI, TBI, AD, AMD, inflammatory aging, stroke, or MS) A method for diagnosing or evaluating patients with this condition involves measuring one or more inflammasome proteins. Based on the observed level, amount, or concentration, alone or in biological samples obtained from patients In combination with one or more control biomarker proteins, inflammation or inflammation-related To determine the presence or absence of a protein signature associated with the disease, disorder, or pathological condition. This includes, in certain embodiments, the protein signature is a small elevated level at least one inflammasome protein and / or at least one elevated level Includes control biomarker proteins. At least one protein signature in the protein signature. One type of inflammasome protein and / or control biomarker protein The level is determined by the presence of at least one type of insect in the biological sample obtained from the control subjects. Lamasome protein and / or at least one control biomarker protein Compared to a quality level or percentage, or to a predetermined reference value further described herein. Alternatively, it may be enhanced compared to the range of the reference value. The control group may be healthy individuals. Normal individuals have inflammation or inflammation-related diseases, disorders, or conditions (e.g., NASH, MCI). (and does not present with symptoms related to AMD, TBI, AD, inflammatory aging, stroke, or MS) It can be an individual. The protein signature is, in certain embodiments, an elevated level of small It may contain at least one type of inflammasome protein. At least one control. Biomarker proteins are expressed at levels that indicate inflammation or inflammation-related diseases, disorders, or It is one of the proteins that has been previously shown to be associated with the disease state. Morphologically, the control biomarker proteins are Gal-3 and CRP (hs-CRP). ), NFL, amyloid-beta (Aβ (1-42) ), T-Tau, sAPPα or sAP It is Pβ. Patients exhibiting a protein signature have inflammation or inflammation-related diseases or disorders. Harm or pathological condition (e.g., NASH, MCI, AD, TBI, AMD, inflammatory aging, stroke) They may be selected or identified as having (or being MS).

[0081] In some embodiments, the measured levels of one or more inflammasome proteins The concentration or amount of one or more control biomass, either alone or in a biological sample. In combination with ker proteins, inflammation or inflammation-related diseases, disorders, or conditions (for example) (e.g., NASH, MCI, TBI, AD, AMD, inflammatory aging, stroke, or MS) Used to create protein profiles or signatures that serve as indicators of disease severity. In some cases, the protein profile is derived from the biological data obtained from the control subjects. The level, abundance, and percentage of one or more inflammasome proteins in the sample. Or in relation to the concentration, or in relation to the range of specified values ​​or reference values ​​described herein, patient The levels of one or more inflammasome proteins measured in biological samples, It may include quantity, percentage, or concentration. In some cases, the protein profile is one or more inflammasome tannins in biological samples obtained from control subjects. Levels, abundances, and pars of protein and one or more control biomarker proteins. In relation to the duration or concentration, or in relation to the range of predetermined values ​​or reference values ​​described herein. Then, one or more inflammasome proteins and The level, abundance, or percentage of one or more control biomarker proteins. This may include concentrations. The control group may be healthy individuals. Healthy individuals may have inflammation or inflammation. Diseases, disorders, or conditions related to (e.g., NASH, MCI, TBI, AD, AMD) It may be an individual that does not exhibit symptoms related to inflammatory aging, stroke, or MS. The control biomarker proteins shown above are those whose expression levels indicate inflammation or inflammation-related diseases. Any protein that has been previously shown to be associated with a disease, disorder, or condition. Obtain. In some embodiments, the control biomarker protein is Gal-3 , CRP (hs-CRP), NFL, amyloid-β (Aβ (1-42) ), T-Tau It is either sAPPα or sAPPβ.

[0082] At least one inflammasome protein and / or control biomarker Protein levels, percentages, or concentrations are measured at a single point in time and at a predetermined reference value or reference. Is it possible to evaluate by comparing it to a range of values, or is it possible to evaluate it at multiple points in time and with a predetermined reference value or in advance? It can be evaluated by comparing it to a valued value.

[0083] Where used herein, “a given reference value” or range of reference values ​​is based on known samples or The inflammasome proteins and / or control biomarker proteins identified from these sources This can mean a predetermined value or range of reference values ​​for the level or concentration of a substance. For example, a predetermined reference value Alternatively, the range of reference values ​​is derived from biological samples obtained from control subjects (i.e., healthy subjects). Inflammasome proteins and / or control biomarker proteins during the pull process It is possible to reflect the level or concentration of the controlled substance in some embodiments. The results may be age-matched to the patients being evaluated. Biological data obtained from patients and control subjects. Both samples are of the same type (e.g., serum or serum-derived extracellular vesicles). It may be an EV. Therefore, in certain embodiments, at least one inflammasome Measured levels of protein and / or control biomarker protein, per The concentration or value is obtained from the control sample (i.e., from a healthy subject). At least one inflammasome protein and / or control biomarker It is compared or determined by the level, percentage, or concentration of the protein. The subject or healthy individual is a disease, disorder, or condition related to inflammation or inflammatory brain injury (for example, Related to NASH, MCI, TBI, AD, stroke, inflammatory aging, AMD, or MS) The subject may not exhibit the symptoms. The control biomarker protein is expressed at a certain level. It could be any of the proteins that have been previously shown to be associated with brain damage. In several embodiments, the control biomarker proteins are GAL-3, CRP( hs-CRP), NFL, amyloid-beta (Aβ)(1-42) ), T-Tau, sAPP It is α or sAPPβ.

[0084] In other embodiments, a predetermined reference value or range of reference values ​​is determined by evaluation using a clinical scale or postmortem analysis. Inflammation or inflammation-related diseases, disorders, or conditions of known severity that are valued (e.g., NA) Patients with SH, MCI, TBI, AD, AMD, inflammatory aging, stroke, or MS Inflammasome proteins and / or control biomass in samples obtained from It can reflect the level or concentration of protein. A given reference value is inframasor Even in known amounts or concentrations of the protein and / or control biomarker protein Possible. Such inflammasome and / or control biomarker proteins Known amounts or concentrations are associated with the controlled population or known levels of inflammation or inflammation. Inflammasomes and / or control from a population of patients with the aforementioned disease, disorder, or condition It may correlate with the average level or concentration of the biomarker protein. In another embodiment, The specified reference value may be a range of values, and may also be, for example, the mean ± standard deviation or a confidence interval. It can represent various levels of inflammation or inflammation-related diseases, disorders or Pathophysiology (e.g., NASH, AD, MCI, TBI, AMD, inflammatory aging, stroke or Specific inflammasomes and / or control biomarkers across the entire severity range of MS - This can also mean individual reference values ​​for proteins. Control biomarker proteins are Current levels may be associated with any of the proteins previously shown to be linked to brain damage. In some embodiments, control biomarker proteins, Gal-3, CR P(hs-CRP), NFL, amyloid-β(Aβ) (1-42) ), T-Tau, sA It is PPα or sAPPβ. In certain embodiments, it is a predetermined reference value or a range of reference values ​​and ratio Each of the inflammasome proteins must be one or more types (e.g., ASC, caspase-1 or IL-18) and / or control biomarker proteins (e.g., Gal-3, CRP (hs-CRP), NFL, sAPPα, sAPPβ, T-Tau, or AB ( 1-42) An increase in the level of ) indicates a more severe form of inflammation or inflammation-related disease, disorder, etc. Alternatively, it can serve as an indicator of a pathological condition (for example, brain injury).

[0085] At least one type of infrastructure detected or measured by any of the methods provided herein The inflammasome protein may be one or more types of inflammasome proteins. In the application morphology, at least one inflammasome protein is involved with multiple inflammasome proteins. It is a protein. Multiple species consist of at least two, three, four, or five types of infrastructure. It may be a masome protein. At least one or more inflammasome proteins. Examples of inflammasome proteins include NAPL1 / NLRP1 and NALP2 / N LRP2, NALP3 / NLRP3, IPAF / NLRC4, AIM2 inflammasome These could be components of any inflammasome known in the art. In combination, at least one inflammasome protein or multiple inflammasome proteins The substance can be a component of a canonical inflammasome or a non-canonical inflammasome. In one embodiment, at least one inflammasome protein is used to recruit caspases. Apoptosis-related speck-like protein (ASC) containing a domain, caspase-1 , interleukin-18 (IL-18) or interleukin-1 beta (IL-1 beta) In one embodiment, at least one inflammasome protein is used. It is an apoptosis-related speck-like protein (ASC) that contains a parase recruitment domain. In one embodiment, at least one inflammasome protein is mediated by caspase-1. Yes. In one embodiment, at least one inflammasome protein is used with IL-18. Yes. At least one type of control detected or measured by any of the methods provided herein. Troll biomarker proteins have been previously shown to have expression levels associated with brain injury. It may be any of the proteins that are present. In one embodiment, at least one control The biomarker protein is Gal-3. In one embodiment, at least one The control biomarker protein is CRP (hs-CRP). In one embodiment, At least one control biomarker protein is NFL. In this embodiment, at least one control biomarker protein is sAPPα In some embodiments, at least one control biomarker protein The substance is sAPPβ. In some embodiments, at least one control agent is used. Omarker proteins include Aβ (1-42) In some embodiments, at least Another type of control biomarker protein is Aβ (1-40) There are several. In this embodiment, at least one control biomarker protein is used in APP. Yes. In some embodiments, at least one control biomarker protein The quality is T-Tau.

[0086] Inflammasome proteins and / or controls of the methods provided herein Omarker proteins (e.g., Gal-3, CRP (hs-CRP), NFL, sAP) Pα, sAPPβ, AB (1-42) (e.g., control biomarker proteins) It can be measured in biological samples by various methods known to those skilled in the art. For example, Tan Proteins are not limited to liquid chromatography, gas chromatography, etc. - Mass spectrometry, immunoassay, radioimmunoassay, immunofluorescence assay, FRET - Assay, immunoblotting, ELISA, liquid chromatography followed by mass spectrometry ( For example, it can be measured by methods such as MALDI-MS. Other suitable for measuring and quantifying any of the specific biomarker proteins of the present invention The method can be verified.

[0087] In one embodiment, at least one of the methods provided herein is detected or measured by any of the following: Also, one type of inflammasome protein or multiple types of inflammasome proteins are immuno Detection or measurement is possible via the use of noassay. In one embodiment, provided herein At least one control biomarker detected or measured by one of the following methods Proteins can be detected or measured through the use of immunoassays. The assay may be any immunoassay known in the art. For example, an immunoassay The assay is performed using an immunoblot, enzyme-linked immunosorbent assay (ELISA), or micro Microfluid immunoassay is possible for use in the method provided herein. An example of a fluid immunoassay is the Simple Plex® Platform (Pro (Tein Simple, San Jose, California)

[0088] Any immunoassays provided herein for use in the methods described herein are inframass Antibodies targeted at inflammasome proteins are available. Examples of inflammasome components include... For example, NAPL1, NALP2, NALP3, NLRC4, AIM2 inflammasome any canonical or non-canonical inflammasome component known in the art This is possible. In one embodiment, the inflammasome protein has a caspase recruitment domain. Apoptosis-related speck-like protein (ASC), caspase-1, and inter - Leukin-18 (IL-18) or interleukin-1 beta (IL-1 beta) Yes. In one embodiment, the inflammasome protein contains a caspase recruitment domain. It is an apoptosis-related speck-like protein (ASC). In one embodiment, The inflammasome protein is caspase-1. In one embodiment, the inflammasome The protein is IL-18. In one embodiment, the inflammasome protein is IL It is -1 beta.

[0089] Any immunoassays provided herein for use in the methods described herein are controls Antibodies targeted at biomarker proteins are available. Omarker proteins include Gal-3, CRP (hs-CRP), NFL, sAPPα, sAPPβ or Aβ (1-42)It is possible.

[0090] Any suitable antibody that specifically binds to ASC is available, for example, custom Alternatively, commercially available ASC antibodies can be used in the methods provided herein. Anti-ASC antibodies are For example, the domain of mammalian ASC proteins such as human or rat ASC proteins. Or it may be an antibody that specifically binds to a part thereof. Antibody for use in the method described herein An example of an ASC antibody is U.S. Patent No. 8685400 (the entire content of which is referenced). This may be found in (and incorporated herein) the methods provided herein. Examples of commercially available anti-ASC antibodies for use include, but are not limited to, 04-1 47 Anti-ASC, clone 2EI-7 mouse monoclonal antibody (Millipore S igma), AB3607-anti-ASC antibody (Millipore Sigma), o rb194021 anti-ASC (manufactured by Biorbyt), LS-C331318-50 anti-ASC (manufactured by LifeSpan Biosciences), AF3805 anti-ASC (R&D S (manufactured by ystems), NBP1-78977 Anti-ASC (Novus Biological (made by s), 600-401-Y67 anti-ASC (Rockland Immunochemi (Manufactured by CALS), D086-3 anti-ASC (Manufactured by MBL International), AL 177 Anti-ASC (Adipogen), Monoclonal Anti-ASC (Clone o93E9 ) antibody, anti-ASC antibody (F-9) (Santa Cruz Biotechnology (Manufactured by Santa Cruz Biotechnology), Anti-ASC antibody (B-3) (Manufactured by Santa Cruz Biotechnology) ), ASC polyclonal antibody-ADI-905-173 (Enzo Life Science) (Manufactured by ences), A161 anti-human ASC (Manufactured by Leinco Technologies) This includes the human ASC protein, with acceptance number NP_037390.2(Q9ULZ 3-1) It may be NP_660183(Q9ULZ3-2) or Q9ULZ3-3. The rat ASC protein may have acceptance number NP_758825 (BAC43754). The mouse ASC protein may have acceptance number NP_075747.3. In this state, the antibody is a PYR of mammalian ASC protein (e.g., human or rat ASC). The IN-PAAD-DAPIN domain (PYD) or a portion or fragment thereof It binds. In this embodiment, the antibody described herein is a PYD of human or rat ASC. At least 65% of the domain or its fragments (e.g., 65, 70, 75) It specifically binds to amino acid sequences having 80-85% sequence identity. In one embodiment, The antibody is the C-terminal casp of the mammalian ASC protein (e.g., human or rat ASC). - It binds to the CARD mobilization domain or a part or fragment thereof. In terms of application, the antibodies described herein are the CARD domain of human or rat ASC or At least 65% (e.g., 65, 70, 75, 80, 85%) of the fragments It specifically binds to an amino acid sequence having sequence identity. In another embodiment, the antibody is The region of rat ASC, for example, the amino acid sequence ALRQTQPYLVTDLEQS(Sequence ID) 1) Specific to rat ASC, residues 178-193 of acceptance number BAC43754 It is an antibody that binds to the target. In this embodiment, the antibody described herein is a rat ASC antibody. At least 65 amino acids relative to the amino acid sequence ALRQTQPYLVTDLEQS (Sequence ID 1) Amino acid sequences having % (for example, 65, 70, 75, 80, 85%) sequence identity are particularly important. In another embodiment, the antibody binds to a region of human ASC, for example, an amino acid sequence. This antibody specifically binds to RESQSYLVEDLERS (SEQ ID NO: 2). Morphologically, the antibodies described herein are based on the amino acid sequence RESQSYLVEDL of human ASC. At least 65% of ERS (Sequence ID 2) (e.g., 65, 70, 75, 80, 80) It specifically binds to amino acid sequences that have 5% sequence identity.

[0091] Any suitable anti-NLRP1 antibody (e.g., commercially available or custom-made) is provided herein. It can be used in the methods described herein. An example of an anti-NLRP1 antibody for use in the methods described herein is: U.S. Patent No. 8,685,400 (the contents of which are incorporated herein by reference in their entirety) It may be found in rare places. Commercial use for use in the manner provided herein. Examples of anti-NLRP1 antibodies include, but are not limited to, human NLRP1 polyclonal antibodies. New antibody AF6788 (manufactured by R&D Systems), EMD Millipore Sagi polyclonal anti-NLRP1 ABF22, Novus Biologicals Sigma-Aldric Polyclonal Anti-NLRP1 NB100-56148 h Mouse Polyclonal Anti-NLRP1 SAB1407151, Abcam Rabbit Polyc Ronal anti-NLRP1 ab3683, Biorbyt rabbit polyclonal anti-NLRP 1 orb325922, my BioSource Rabbit Polyclonal Anti-NLRP1 MBS7001225, R&D systems Sheep Polyclonal AF6788, Aviva Systems Mouse Monoclonal Anti-NLRP1 oaed00344 Aviva Systems Sagi Polyclonal Anti-NLRP1 ARO54478_P0 50, Origene Rabbit Polyclonal Anti-NLRP1 APO7775PU-N, A ntibodies online Rabbit Polyclonal Anti-NLRP1 ABIN768 983, Prosci Rabbit Polyclonal Anti-NLRP1 3037, Protein ech Rabbit Polyclonal Anti-NLRP1 12256-1-AP, Enzo Mouse Mono Clonal anti-NLRP1 ALX-804-803-C100, Invitrogen Mouse Monoclonal Anti-NLRP1 MA1-25842, GeneTex Mouse Monoclonal -Natural anti-NLRP1 GTX16091, Rockland Rabbit Polyclonal Anti-NL RP1 200-401-CX5 or Cell Signaling Technolo One example is the GY rabbit polyclonal anti-NLRP1 4990. Human NLRP1 protein The quality is as follows: acceptance numbers AAH51787, NP_001028225, NP_055737, It could be NP_127497, NP_127499, or NP_127500. One implementation form In this state, the antibody is a Pyri of the mammalian NLRP1 protein (e.g., human NLRP1). n, NACHT, LRR1-6, FIIND, or CARD domain or a portion thereof or binds to a fragment. In this embodiment, the antibody described herein is human NL RP1 specific domains (e.g., Pyrin, NACHT, LRR1-6, FIIND) Or CARD) or at least 65% (for example, 65%) of those fragments. It specifically binds to amino acid sequences that have sequence identity of %, 70%, 75%, 80%, and 85%. In one embodiment, custom design and The manufactured chicken anti-NLRP1 polyclonal antibody is available. This antibody is used by The following amino acid sequence of NLRP1: CEYYTEIREREREKSEKGR (sequence number) It may target item 3). In one embodiment, the antibody is an amino acid sequence of SEQ ID NO: 3 or MEE At least 85% of SQS KEE SNT EG-cys (SEQ ID NO: 4) It specifically binds to amino acid sequences that have sequence identity.

[0092] Whether custom-made or commercially available, any suitable antibody that specifically binds to caspase-1 is, It can be used in the methods provided herein. An example of a commercially available anti-caspase-1 antibody is R&D Systems: Cat# MA B6215 or Cat#AF6215, Cell Signaling:Cat#386 6, #225 or #4199, Novus Biologicals: Cat#NB10 0-56565, #NBP1-45433, #NB100-56564, #MAB621 5, #AF6215, #NBP2-67487, #NBP2-15713, #NBP2- 15712, #NBP1-87680, #NB120-1872, #NBP1-7660 Examples include 5 or #H00000834-M01.

[0093] Whether custom-made or commercially available, any suitable antibody that specifically binds to caspase-8 is, It can be used in the methods provided herein. Examples of commercially available anticaspase-8 antibodies include Abcam:Cat#ab25901, a b227430, ab108333, ab220171, ab4052, ab23194 8, ab32397, ab61755, ab138485, ab 208774, ab3 2125, ab231475, ab247233, ab2553, ab232046, a b194145 or ab119809, Novus Biologicals:Cat# NB100-56116, #NB100-56527, #NBP1-05123, #AF 705, #AF1650, #MAB704, #NBP2-15722, #NBP1-76 610, #NBP2-22183, #NBP2-67803, #NB500-208 or # NBP2-67355, Santa Cruz Biotechnology Cat# 8CSP03, Cell Signaling Technology:Cat.#47 Examples include #90 or #9746.

[0094] Whether custom-made or commercially available, suitable antibodies that specifically bind to caspase-11 are all It can be used in the methods provided herein. An example of a commercially available anti-caspase-11 antibody is Abcam:Cat#ab18067 3, ab240991, ab22684 or ab69540, Novus Biolog ical Cat#NB120-10454, Cell Signaling Tech Nology Cat#14340 or ThermoFisher Cat#14-99 35-82 are listed.

[0095] Whether custom-made or commercially available, suitable antibodies that specifically bind to IL-18 are all available from Honmei. It can be used in the manner provided in this specification. An example of a commercially available anti-IL-18 antibody is R&D Systems: Cat#D044-3. Cat#D045-3, #MAB646, #AF2548, #D043-3, #MAB2 548, MAB9124, #MAB91241, #MAB91243, MAB91244 Alternatively, #MAB91242, Novus Biologicals:Cat#AF2548 , #D043-3, #MAB2548, #MAB9124, #MAB91243, #MA B91244, #MAB91241, #D045-3, #MAB91242 or #D04 4-3 are mentioned.

[0096] Whether custom-made or commercially available, any suitable antibody that specifically binds to IL-1 beta is, It can be used in the methods provided herein. An example of a commercially available anti-IL-18 antibody is R&D Systems: Cat#MAB60 1, Cat#MAB201, #MAB6964, #MAB601R, #MAB8406 or #MAB6215, Cell Signaling:Cat#31202, #6312 4. #12426 or #12507, Novus Biologicals: Cat#A F-201-NA, #NB600-633, #MAB201, #MAB601, #NBP 1-19775, #NBP2-27345, #AB-201-NA, #NBP2-273 42, #NBP2-67865, #NBP2-27343, #NBP2-27340, # NBP2-27340, #NB120-8319, #23600002, #MAB840 6. #NB100-73053, #NB120-10749, or #MAB601R are listed. It is possible.

[0097] Any suitable antibody that specifically binds to NFL, whether custom-made or commercially available, is specified herein. It can be used in the methods provided herein. Commercially available for use in the methods provided herein An example of an anti-NFL antibody is Boster Bio:Cat#MA1070;BioLe gend:Cat#837801;R&D Systems:Cat#MAB2216, #MAB22162, Novus Biologicals:#NB300-131 or #NBP2-31201 is an example of an anti-N compound for use in the manner provided herein. Another example of fl antibodies is anti-Nf prepared by Uman Diagnostics. One example is the l antibody.

[0098] Any suitable antibody that specifically binds to APP, whether custom-made or commercially available, is specified herein. It can be used in the methods provided herein. Commercially available for use in the methods provided herein An example of an anti-APP antibody is the United States Biological: Ca t#303112;St.John's Laboratory:Cat#STJ113 456;Biorbyt:Cat#orb223652, Cat#orb223651, United States Biological:Cat#253944(Cat# 253943) is one example.

[0099] Whether custom-made or commercially available, suitable antibodies that specifically bind to Gal-3 are all available at Honmei. It can be used in the manner provided in this specification. Examples of commercially available anti-Gal-3 antibodies include Abcam Cat#ab209344 and ab76. 466, ab76245, ab2785 and ab31707, Santa Cruz B iotechnology:Cat#sc-23938, Novus Biologic al:Cat#AF1197, Cat#AF1154, Cat#NB300-538, C at#NBP1-92690, Cat#MAB1197, Cat#NBP2-16589 And Cat#MAB11541 is an example.

[0100] Any suitable antibody that specifically binds to CRP, whether custom-made or commercially available, is specified herein. It can be used in the methods provided herein. Commercially available for use in the methods provided herein Examples of anti-CRP antibodies include Abcam Cat#ab32412, ab256492, ab256525, ab207756 and ab51016, HyTest Ltd ca Examples include t#4C28-C6 and Genescript cat#hsCRP(11C2). It can be done.

[0101] A method for determining the specificity and affinity of monoclonal antibodies by competitive inhibition is Harlo. w,et al.,Antibodies:A Laboratory Manual, Cold Spring Harbor Laboratory Press,Cold Spring Harbor, NY, 1988, Colligan et al. ,eds.,Current Protocols in Immunology,Gr. eene Publishing Assoc.and Wiley Intersci ence, NY, (1992, 1993) and Muller, Meth. Enzym ol.92:589-601,1983 (These references are entirely referenced in this specification.) It can be found in (which is incorporated into).

[0102] The present invention provides anti-inflammasome (e.g., anti-ASC and anti-NLRP1) and / or anti-con Troll biomarker protein antibodies are polypeptides or antigens in appropriate animals. Fragment inoculation, in vitro stimulation of lymphocyte populations, synthesis methods, hybridomas and / or nucleic acids encoding such anti-ASC, anti-NFL, anti-sAPPα / β, and anti-NLRP1 antibodies It can be routinely produced by methods such as recombinant cells that express this gene, but is not limited to these methods. It is not a purified recombinant ASC or its peptide fragment, for example, rat ASC. Residues 178-193 (SEQ ID NO: 1) of C (e.g., acceptance number BAC43754) or human Immunization of animals using ASC SEQ ID NO: 2 is an example of a method for preparing anti-ASC antibodies. Similarly, purified recombinant NLRP1 or its peptide fragments, such as rat NALP1 The residues MEE SQS KEE SNT EG-cys (SEQ ID NO: 4) or human NALP Immunization of animals using Sequence ID No. 3 of 1 is an example of a method for preparing anti-NLRP1 antibodies.

[0103] Monochromes that specifically bind to ASC, NLRP1, sAPPα, sAPPβ, or NFL. A non-alcoholic antibody can be obtained by methods known to those skilled in the art. For example, Kohler a nd Milstein, Nature 256:495-497, 1975, U.S. Patent No. 4,376,110, Ausubel et al., eds., Curre. nt Protocols in Molecular Biology,Greene Publishing Assoc.and Wiley Interscience ,NY,(1987,1992), Harlow and Lane ANTIBO DIES:A Laboratory Manual Cold Spring Har bor Laboratory Press,Cold Spring Harbor, NY, 1988, Colligan et al., eds., Current Pro. tocols in Immunology,Greene Publishing A ssoc. and Wiley Interscience, NY, (1992, 1999 3) See (the contents thereof are incorporated herein by reference in their entirety). The body contains IgG, IgM, IgE, IgA, GILD and any of their subclasses. Furthermore, it may be of any of the immunoglobulin classes. The monoclonal anti Hybridomas that produce bodies can be cultured in vitro, in situ, or in vivo. ru.

[0104] In some cases, the methods provided herein are at least about 70%, at least about 7 1%, at least about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 7 8%, approximately 79%, approximately 80%, approximately 81%, approximately 82%, approximately 83%, approximately 84%, approximately 85%, approximately 8 6%, approximately 87%, approximately 88%, approximately 89%, approximately 90%, approximately 91%, approximately 92%, approximately 93%, approximately 9 Prediction success rates of 4%, approximately 95%, approximately 96%, approximately 97%, approximately 98%, approximately 99%, and up to 100%. And, inflammation or diseases, disorders, or conditions caused by or related to inflammation (for example, NASH, Diagnosing or detecting AD, MCI, AMD, inflammatory aging, stroke, MS, or TBI. They may have the ability.

[0105] In some cases, the methods provided herein are at least about 70%, at least about 7 1%, at least about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 7 8%, approximately 79%, approximately 80%, approximately 81%, approximately 82%, approximately 83%, approximately 84%, approximately 85%, approximately 8 6%, approximately 87%, approximately 88%, approximately 89%, approximately 90%, approximately 91%, approximately 92%, approximately 93%, approximately 9 Sensitivity and / or up to 100%: 4%, approximately 95%, approximately 96%, approximately 97%, approximately 98%, approximately 99%, and 100% Or, by specificity, a disease, disorder, or condition caused by or related to inflammation (for example, Diagnosing NASH, MCI, stroke, MS, AMD, inflammatory aging, AD, or TBI) It may have the ability to detect it.

[0106] In one embodiment, the disease, disorder, or condition caused by or related to inflammation is brain injury. In the treatment configuration, brain injury is MS, and the controls provided herein (e.g., predetermined) Elevated AS levels in serum obtained from patients compared to the reference value or range of reference values. Detection of C indicates that patients have at least 75%, 80%, 90%, 95%, 99%, or 100% It is determined to have MS by sensitivity. In another embodiment, brain injury is MS, and according to this specification Compared to the control provided (e.g., a given reference value or range of reference values), the patient's... The detection of elevated levels of ASC in the obtained serum indicated that at least 75% of patients had It is determined that the MS has a specificity of 80%, 85%, 90%, 95%, 99%, or 100%. The predetermined reference values ​​in these embodiments may be the cutoff values ​​shown in Table 7. In yet another embodiment, the brain injury is MS, and the control provided herein ( For example, an increase in serum obtained from a patient compared to a predetermined reference value or range of reference values. With the detection of ASC at this level, patients have at least 90% sensitivity and at least 80% It is determined that it has MS in specificity. The predetermined reference values ​​in this embodiment are shown in Table 7. This could be a cutoff value. In some cases, the range of the reference value is at least 90% sensitivity. To achieve a specificity of at least 80%, use approximately 300 pg / ml to approximately 340 pg / ml. It is possible.

[0107] In one embodiment, the brain injury is a stroke, and the controls provided herein (for example) If the elevated meter reading in the serum obtained from the patient is compared to a predetermined reference value or range of reference values, Bell's ASC detection indicates that patients are at least 75%, 80%, 90%, 95%, 99%, or It is determined with 100% sensitivity that the person has suffered a stroke. In another embodiment, brain injury is Stroke, and the controls provided herein (e.g., a predetermined reference value or reference value The detection of elevated levels of ASC in serum obtained from patients compared to the normal range indicates that patients Those who have at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% of the unique characteristics It is determined that it has MS in degrees. The predetermined reference values ​​in these embodiments are shown in Table 8. This may be a cutoff value. In another embodiment, the brain injury is a stroke, which is described herein. Compared to the provided control (e.g., a predetermined reference value or range of reference values), the values ​​obtained from the patient are obtained. The detection of elevated levels of ASC in the serum indicates that the patient has at least 100% The patient is determined to have suffered a stroke with sensitivity and specificity of at least 90%. The specified reference value may be the cutoff value shown in Table 8. In some cases, the reference value The range is approximately to achieve at least 100% sensitivity and at least 90% specificity. It can range from 380 pg / ml to approximately 405 pg / ml. Stroke is provided herein. It may be ischemic or hemorrhagic.

[0108] In one embodiment, the brain injury is a stroke, and the controls provided herein (for example) If the elevated meter reading in the serum obtained from the patient is compared to a predetermined reference value or range of reference values, Bell's ASC detection indicates that patients have at least 75%, 80%, 85%, 90%, and 95% of cases. A stroke is determined with a sensitivity of %, 99%, or 100%. In another embodiment, Brain injury is a stroke, and the controls provided herein (e.g., specified reference) The elevated level of ASC in the serum obtained from the patient compared to the value or range of the reference value. Detection indicates that the patient has at least 75%, 80%, 90%, 95%, 99%, or 100% of the characteristic It is determined that the MS has different degrees. The predetermined reference values ​​in these embodiments are shown in Table 9. This may be a cutoff value. In another embodiment, the brain injury is a stroke, and this specification Compared to the provided control (e.g., a given reference value or range of reference values), the patient's The detection of elevated levels of ASC in the obtained serum-derived EV indicates that the patient has at least It is determined with 100% sensitivity and at least 90% specificity that the person has suffered a stroke. In some embodiments, the predetermined reference value may be the cutoff value shown in Table 9. In addition, the range of the reference value achieves at least 100% sensitivity and at least 90% specificity. The concentration may be approximately 70 pg / ml to approximately 90 pg / ml. Stroke is provided herein. It can be ischemic or hemorrhagic.

[0109] In one embodiment, the brain injury is TBI, and the controls provided herein (e.g.) The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of ASC in the patient indicates that at least 75%, 80%, 90%, 95%, 99%, or 1% of patients are affected. It is determined to have TBI with 00% sensitivity. In another embodiment, brain injury is TBI and compared with the controls provided herein (e.g., a predetermined reference value or range of reference values) In contrast, the detection of elevated levels of ASC in serum obtained from patients indicated that fewer patients had the condition. TBI was detected with specificity of 75%, 80%, 85%, 90%, 95%, 99%, or 100%. It is determined that it has. The predetermined reference values ​​in these embodiments are shown in Table 16. It may be a value. In yet another embodiment, the brain injury is TBI, and provided herein Compared to a control (e.g., a predetermined reference value or range of reference values), the results obtained from the patient are obtained. The detection of elevated levels of ASC in the serum indicates that patients have at least 90% sensitivity and It is determined to have TBI with a specificity of at least 80%. A predetermined reference in this embodiment The value may be the cutoff value shown in Table 16. In some cases, the range of the reference value is small. To achieve at least 80% sensitivity and at least 70% specificity, approximately 275 pg / m² is required. It can be approximately 450 pg / ml.

[0110] In one embodiment, the brain injury is TBI, and the controls provided herein (e.g.) The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of caspase-1 in patients indicates that at least 75%, 80%, 90%, 95%, and 99% of patients have caspase-1. It is determined to have TBI with a sensitivity of % or 100%. In another embodiment, brain injury is T BI is a control provided herein (for example, a predetermined reference value or a range of reference values). By detecting elevated levels of caspase-1 in serum obtained from patients (compared to the surrounding area), And the patients had at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is determined that it has TBI in specificity. The predetermined reference values ​​in these embodiments are shown in Table 15. The cutoff value shown may be the indicated value. In yet another embodiment, the brain injury is TBI, Compared with the controls provided herein (e.g., a given reference value or range of reference values) The detection of elevated levels of caspase-1 in serum obtained from patients indicated that the patients were small It is determined to have TBI with at least 90% sensitivity and at least 80% specificity. The predetermined reference values ​​in the embodiments may be the cutoff values ​​shown in Table 15. In this case, the range of the reference value must achieve at least 70% sensitivity and at least 75% specificity. Therefore, the concentration can range from approximately 2.812 pg / ml to approximately 1.853 pg / ml.

[0111] In one embodiment, the brain injury is MCI, and the controls provided herein (e.g., The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of ASC in the patient indicates that at least 75%, 80%, 85%, 90%, and 95% of patients... It is determined with 99% or 100% sensitivity that the patient has MCI. In another embodiment, brain injury This is an MCI, and the controls provided herein (e.g., a predetermined reference value or reference value) The detection of elevated levels of ASC in serum obtained from patients compared to the range indicated that At least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% of patients It is determined that the individual has MCI with specificity of 90%, 95%, 99%, or 100%. The predetermined reference values ​​in the embodiment may be the cutoff values ​​shown in Tables 22A and 23. In another embodiment, the brain injury is MCI, and the control provided herein ( For example, an increase in serum obtained from a patient compared to a predetermined reference value or range of reference values. With the detection of ASC at this level, patients have at least 90% sensitivity and at least 70% It is determined that it has MCI in terms of specificity. The predetermined reference values ​​in this embodiment are shown in Table 22A and The cutoff value may be as shown in 23. In some cases, the range of the reference value is at least To achieve 90% sensitivity and at least 70% specificity, approximately 257 pg / ml to approximately 3 It can be 42 pg / ml. In some cases, the cutoff value is greater than 560 pg / ml. .

[0112] In one embodiment, the brain injury is MCI, and the controls provided herein (e.g., The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of IL-18 in the patient indicates that at least 75%, 80%, 85%, 90%, and 95% of patients are affected. It is determined that it has MCI with a sensitivity of %, 99%, or 100%. In another embodiment, Brain injury is MCI, and the controls provided herein (e.g., a given reference value or Elevated levels of IL-18 in serum obtained from patients compared to the reference range. Based on the results, the percentage of patients was at least 50%, 55%, 60%, 65%, 75%, 80%, and 85%. These are determined to have MCI with specificity of 90%, 95%, 99%, or 100%. The predetermined reference values ​​in the embodiment may be the cutoff values ​​shown in Tables 22A and 25. In yet another embodiment, the brain injury is MCI, and the control provided herein (For example, an increase in serum obtained from a patient compared to a predetermined reference value or range of reference values) The detection of IL-18 at this level indicates that patients have at least 70% sensitivity and at least 5 It is determined to have MCI with a specificity of 5%. The predetermined reference values ​​in this embodiment are shown in Table 22. The cutoff values ​​may be those shown in A and 25. In some cases, the range of the reference value is less Approximately 200 pg / ml is needed to achieve a sensitivity of at least 70% and a specificity of at least 50%. It is approximately 214 pg / ml.

[0113] In one embodiment, the brain injury is MCI, and the controls provided herein (e.g., The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of caspase-1 in the patient indicates that at least 55%, 60%, 65%, and 70% of patients... MCI has a sensitivity of 75%, 80%, 85%, 90%, 95%, 99%, or 100%. It is determined that the brain injury is MCI, and the components provided herein Serum obtained from patients compared to a trol (e.g., a predetermined reference value or range of reference values) The detection of elevated caspase-1 levels indicates that at least 40%, 45%, of the patients 50%, 55%, 60%, 65%, 75%, 80%, 85%, 90%, 95%, 99% or It is determined to have MCI with 100% specificity. A predetermined reference value in these embodiments This may be the cutoff value shown in Table 22A. In yet another embodiment, brain injury is MCI is a control provided herein (for example, a predetermined reference value or reference value Compared to the range, the detection of elevated levels of caspase-1 in serum obtained from patients Therefore, patients have MCI with at least 65% sensitivity and at least 40% specificity. Determined. The predetermined reference value in this embodiment is the cutoff value shown in Table 22A. Obtain. In some cases, achieve at least 65% sensitivity and at least 40% specificity. A reference value of approximately 1.75 pg / ml is used for this purpose.

[0114] In one embodiment, the brain injury is MCI, and the controls provided herein (e.g., The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of IL-1β in the patient indicates that at least 55%, 60%, 65%, 70%, and 75% of patients are affected. It is determined that MCI is present with a sensitivity of %, 80%, 85%, 90%, 95%, 99%, or 100%. It is determined. In another embodiment, the brain injury is MCI, and the control provided herein Compared to a given reference value or range of reference values, the serum obtained from the patient The detection of elevated levels of IL-1β indicates that at least 40%, 45%, or 50% of patients have the condition. 55%, 60%, 65%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is determined that it has MCI with a specificity of %. The predetermined reference values ​​in these embodiments are shown in Table 2. The cutoff value may be shown in 2A. In yet another embodiment, brain injury is MCI Yes, and the controls provided herein (e.g., a given reference value or range of reference values) By comparing the results, the detection of elevated levels of IL-1β in the serum obtained from the patients indicated that the patients It is determined to have MCI with at least 65% sensitivity and at least 55% specificity. The predetermined reference values ​​in this embodiment may be the cutoff values ​​shown in Table 22A. In that case, to achieve at least 65% sensitivity and at least 50% specificity, approximately 0 A reference value of 0.684 pg / ml is used.

[0115] In one embodiment, the brain injury is MCI, and the controls provided herein (e.g., The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of sAPPα in the patient indicates that at least 75%, 80%, 85%, 90%, and 95% of patients are affected. It is determined that the patient has MCI with a sensitivity of %, 97%, 98%, 99%, or 100%. In this embodiment, the brain injury is MCI, and the controls provided herein (e.g., Elevated levels in serum obtained from patients compared to a set reference value or range of reference values. Detection of sAPPα indicates that at least 70%, 75%, 80%, 85%, and 90% of patients have the condition. It is determined that it has MCI with a specificity of 95%, 99%, or 100%. These embodiments The specified reference value may be the cutoff value shown in Table 22A. In this case, the brain injury is MCI, and the controls provided herein (e.g., a predetermined reference) Elevated levels of sAP obtained from patients in serum compared to the range of the reference value or reference value. Detection of Pα indicates that patients have MC with at least 95% sensitivity and at least 70% specificity. It is determined that it has I. The predetermined reference values ​​in this embodiment are the cuts shown in Table 22A. It may be an off value. In some cases, at least 95% sensitivity and at least 70% characteristics A reference value of approximately 1.39 ng / mL is used to achieve the required level of differential.

[0116] In one embodiment, the brain injury is MCI, and the controls provided herein (e.g., The elevated level in serum obtained from the patient compared to a predetermined reference value or range of reference values. Detection of sAPPβ in the patient indicates that at least 75%, 80%, 85%, 90%, and 95% of patients are affected. It is determined that MCI is present with a sensitivity of %, 99%, or 100%. In another embodiment, the brain Damage is MCI, and the controls provided herein (e.g., a given reference value or reference) Detection of elevated sAPPβ levels in serum obtained from patients compared to the irradiance range. Therefore, patients have a success rate of at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is determined that it has MCI with a specificity of %. The predetermined reference values ​​in these embodiments are shown in Table 2. The cutoff value may be shown in 2A. In yet another embodiment, brain injury is MCI Yes, and the controls provided herein (e.g., a given reference value or range of reference values) By detecting elevated levels of sAPPβ in serum obtained from patients, it was determined that the patients It is determined to have MCI with at least 90% sensitivity and at least 75% specificity. The predetermined reference values ​​in this embodiment may be the cutoff values ​​shown in Table 22A. In that case, to achieve at least 90% sensitivity and at least 75% specificity, approximately 0 A reference value of 0.26 ng / mL is used.

[0117] In another embodiment, the brain injury is MCI, and the controls provided herein (e.g.) For example, elevated serum levels obtained from patients compared to a predetermined reference value or range of reference values. Detection of NFL at levels of 55%, 60%, 65%, 70%, and 75% of patients. It is determined that MCI is present with a sensitivity of %, 80%, 85%, 90%, 95%, 99%, or 100%. It is determined. In another embodiment, the brain injury is MCI, and the control provided herein Compared to a given reference value or range of reference values, the serum obtained from the patient The detection of elevated levels of NFL indicates that at least 50%, 55%, 60%, and 65% of patients are at least 65%. With specificity of %, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is determined that it has MCI. The predetermined reference values ​​in these embodiments are shown in Table 22A. This may be a cutoff value. In yet another embodiment, the brain injury is MCI, and this specification Compared to the control provided in the book (e.g., a specified reference value or range of reference values), the patient Detection of elevated levels of NFL in serum obtained from [source] indicates that at least 70% of patients It is determined to have MCI with sensitivity and specificity of at least 75%. The specified reference value may be the cutoff value shown in Table 22A. In some cases, less To achieve a sensitivity of 70% and a specificity of at least 75%, approximately 24 pg / mL is used. The illumination value is used.

[0118] In one embodiment, the brain injury is AD, and the controls provided herein (e.g., Elevated levels in serum obtained from patients compared to a specified reference value or range of reference values. Detection of ASC indicates that at least 75%, 80%, 85%, 90%, 95%, and 9% of patients have ASC. It is determined to have AD with a specificity of 9% or 100%. In another embodiment, brain injury is AD is an AD, and the controls provided herein (for example, a predetermined reference value or a range of reference values) The detection of elevated levels of ASC in serum obtained from patients compared to the surrounding area indicates that patients At least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% It is determined to have AD with specificity of %, 95%, 99%, or 100%. These implementations The predetermined reference value in this state may be the cutoff value shown in Table 22B. Furthermore, another implementation Morphologically, the brain injury is AD, and the controls provided herein (e.g., a specified reference) Elevated ASC levels in serum obtained from patients compared to the range of the reference value or reference value. Detection indicates that the patient has AD with at least 80% sensitivity and at least 70% specificity. This is then determined. The predetermined reference value in this embodiment is the cutoff value shown in Table 22B. It is possible. In some cases, with a reference value of approximately 259 pg / mL, the sensitivity is at least 80%. And it is possible to achieve a specificity of at least 70%. In some cases, the diagnosis of AD vs. MCI. The cutoff value for this is greater than 264.9 pg / ml and less than 560 pg / ml.

[0119] In one embodiment, the brain injury is AD, and the controls provided herein (e.g., Elevated levels in serum obtained from patients compared to a specified reference value or range of reference values. Detection of IL-18 indicates that at least 65%, 70%, 75%, 80%, and 85% of patients have had the disease. It is determined to have AD with a sensitivity of 90%, 95%, 99%, or 100%. Morphologically, the brain injury is AD, and the controls provided herein (e.g., a specified reference) Elevated levels of IL- in serum obtained from patients compared to the range of the reference value or reference value. Based on 18 detections, the percentage of patients was at least 40%, 45%, 50%, 55%, 60%, and 65%. , has AD with specificity of 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is determined that the predetermined reference values ​​in these embodiments are the cutoff values ​​shown in Table 22B. It can be a value. In yet another embodiment, the brain injury is AD, which is provided herein. Blood obtained from patients compared to a control (e.g., a predetermined reference value or range of reference values) The detection of elevated levels of IL-18 in the patient indicates that the patient has at least 70% sensitivity and It is determined to have AD with a specificity of at least 40%. A predetermined reference value in this embodiment. This may be the cutoff value shown in Table 22B. In some cases, at least 70% A reference value of approximately 196 pg / ml is used to achieve sensitivity and at least 40% specificity. It will be done.

[0120] In one embodiment, the brain injury is AD, and the controls provided herein (e.g., Elevated levels in serum obtained from patients compared to a specified reference value or range of reference values. Detection of caspase-1 indicates that at least 55%, 60%, 65%, 70%, and 7% of patients have caspase-1. It is determined that it has AD with sensitivity of 5%, 80%, 85%, 90%, 95%, 99%, or 100%. It is determined. In another embodiment, the brain injury is AD, and the control provided herein Compared to a given reference value or range of reference values, the upper limit in serum obtained from patients Detection of elevated caspase-1 levels indicates that at least 40%, 45%, and 50% of patients have elevated caspase-1 levels. , 55%, 60%, 65%, 75%, 80%, 85%, 90%, 95%, 99%, or 10 It is determined to have AD with a specificity of 0%. The predetermined reference values ​​in these embodiments are shown in Table 2. The cutoff value may be shown in 2B. In yet another embodiment, the brain injury is AD. and compared with the controls provided herein (e.g., a predetermined reference value or range of reference values) In comparison, the detection of elevated levels of caspase-1 in serum obtained from patients indicated that patients It is determined to have AD with a sensitivity of at least 65% and a specificity of at least 55%. The predetermined reference values ​​in this embodiment may be the cutoff values ​​shown in Table 22B. In that case, to achieve at least 65% sensitivity and at least 55% specificity, approximately 1 A reference value of 0.78 pg / ml is used.

[0121] In one embodiment, the brain injury is AD, and the controls provided herein (e.g., Elevated levels in serum obtained from patients compared to a specified reference value or range of reference values. Detection of IL-1β indicates that at least 55%, 60%, 65%, 70%, and 75% of patients have the condition. It was determined to have AD with a sensitivity of 80%, 85%, 90%, 95%, 99%, or 100%. In another embodiment, the brain injury is AD, and the control provided herein ( For example, an increase in serum obtained from a patient compared to a predetermined reference value or range of reference values. Detection of IL-1β at these levels indicates that at least 40%, 45%, 50%, and 55% of patients have IL-1β. , 60%, 65%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% special It is determined that it has AD at different degrees. The predetermined reference values ​​in these embodiments are shown in Table 22B. This may be the cutoff value. In yet another embodiment, the brain injury is AD, and the present Compared to the control provided in the document (e.g., a specified reference value or range of reference values), the patient Detection of elevated levels of IL-1β in serum obtained from the patient indicated that the patient had at least It is determined to have AD with a sensitivity of 65% and a specificity of at least 55%. The specified reference value may be the cutoff value shown in Table 22B. In some cases, To achieve at least 75% sensitivity and at least 40% specificity, approximately 0.693 pg is needed. The reference value for / ml is used.

[0122] In one embodiment, the brain injury is AD, and the controls provided herein (e.g., Elevated levels in serum obtained from patients compared to a specified reference value or range of reference values. Detection of sAPPα indicates that at least 75%, 80%, 85%, 90%, and 95% of patients have the condition. It is determined with 99% or 100% specificity that the patient has AD. In another embodiment, brain injury The scratch is AD, and the control provided herein (e.g., a given reference value or reference value) By comparing the range with the detection of elevated sAPPα levels in serum obtained from patients, And the patients had at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is determined that it has AD in terms of specificity. The predetermined reference values ​​in these embodiments are shown in Table 22B. The cutoff value shown may be the one indicated. In yet another embodiment, the brain injury is AD, and this Compared to the controls provided in the specification (e.g., a given reference value or range of reference values) The detection of elevated levels of sAPPα in serum obtained from patients indicates that at least some patients It is determined to have AD with 90% sensitivity and at least 90% specificity. The predetermined reference value in this state may be the cutoff value shown in Table 22B. In some cases, Approximately 2.5 ng / A reference value in mL is used.

[0123] In another embodiment, the brain injury is AD, and the controls provided herein (for example) If the elevated meter reading in the serum obtained from the patient is compared to a predetermined reference value or range of reference values, Bell's sAPPβ detection indicates that at least 75%, 80%, 85%, 90%, and 9% of patients have sAPPβ. It is determined to have AD with specificity of 5%, 99%, or 100%. In another embodiment, Brain injury is AD, and the controls provided herein (e.g., a given reference value or reference) Detection of elevated sAPPβ levels in serum obtained from patients compared to the irradiance range. Therefore, patients have a success rate of at least 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is determined that it has AD with a specificity of %. The predetermined reference values ​​in these embodiments are shown in Table 22. This could be the cutoff value shown in B. and comparison with a control provided herein (e.g., a predetermined reference value or range of reference values). The detection of elevated levels of sAPPβ in serum obtained from patients indicated that the number of patients was small. It is determined to have AD with at least 80% sensitivity and at least 80% specificity. The specified reference value in the application configuration may be the cutoff value shown in Table 22B. In total, to achieve at least 80% sensitivity and at least 80% specificity, approximately 0.29 A reference value in ng / mL is used.

[0124] In one embodiment, the brain injury is AD, and the controls provided herein (e.g., Elevated levels in serum obtained from patients compared to a specified reference value or range of reference values. NFL detection indicates that at least 55%, 60%, 65%, 70%, 75%, and 8% of patients have the condition. It is determined that the patient has AD with specificity of 0%, 85%, 90%, 95%, 99%, or 100%. In another embodiment, the brain injury is AD, and the controls provided herein (e.g.) For example, elevated serum levels obtained from patients compared to a predetermined reference value or range of reference values. Detection of NFL at levels of 50%, 55%, 60%, 65%, and 70% of patients AD has specificity of %, 75%, 80%, 85%, 90%, 95%, 99%, or 100%. The predetermined reference values ​​in these embodiments are shown in Table 22B. It may be a value. In yet another embodiment, the brain injury is AD, and provided herein Compared to a control (e.g., a predetermined reference value or range of reference values), the results obtained from the patient were obtained. Detecting elevated levels of NFL in serum allows patients to have at least 60% sensitivity and low At the very least, it is determined that it has AD with a specificity of 55%. The predetermined reference value in this embodiment is These may be the cutoff values ​​shown in Table 22B. In some cases, at least 60% sensitivity A reference value of approximately 21.4 pg / mL is used to achieve a specificity of at least 55%. It will be done.

[0125] In one embodiment, MCI and AD in brain injury are compared using serum obtained from MCI patients versus AD patients. They can be distinguished by comparing the ASC levels within them (for example, a predetermined reference value or reference). (Range of illumination values). In some embodiments, the method is at least 70%, 75%, 80% With sensitivity of 85%, 90%, 95%, 99%, or 100%, the patient's brain injury (e.g., AD or This determines the MCI. In another embodiment, this method determines at least 60%, 65%, and 7%. Patients with specificity of 0%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% To determine brain injury (e.g., AD or MCI). The predetermined reference values ​​in these embodiments are: The cutoff values ​​may be those shown in Table 22C. In yet another embodiment, this method is less Based on the level of ASC, the patient should have at least 70% sensitivity and at least 60% specificity. Determine the type of brain injury (e.g., AD or MCI). The predetermined reference values ​​in this embodiment are shown in Table 2. The cutoff value may be shown in 2C. In some cases, the reference value is approximately 560 pg / mL. Therefore, it is possible to achieve a sensitivity of at least 70% and a specificity of at least 60%.

[0126] In one embodiment, MCI and AD in brain injury are compared using serum obtained from MCI patients versus AD patients. They can be distinguished by comparing the levels of caspase-1 inside (for example, by a given reference). (Range of value or reference value). In some embodiments, the method is at least 70%, 75% , with sensitivity of 80%, 85%, 90%, 95%, 99%, or 100% for the patient's brain injury (e.g.) Determine AD or MCI. In another embodiment, the method determines at least 60%, 6 Specificity of 5%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% This determines the patient's brain injury (e.g., AD or MCI). In these embodiments, a predetermined reference is used. The illumination value may be the cutoff value shown in Table 22C. In yet another embodiment, The method measures caspase-1 levels with at least 70% sensitivity and at least 60% specificity. Based on this, the patient's brain injury (e.g., AD or MCI) is determined. The reference value can be the cutoff value shown in Table 22C. In some cases, it is approximately 1.94 With a reference value of pg / mL, it is possible to achieve a sensitivity of at least 70% and a specificity of at least 60%. It is Noh.

[0127] In one embodiment, MCI and AD in brain injury are compared using serum obtained from MCI patients versus AD patients. They can be distinguished by comparing the levels of IL-18 inside (for example, a predetermined reference value or (where is the range of the reference value). In some embodiments, the method is at least 70%, 75%, 8 Patient brain injury (e.g., A) with sensitivity of 0%, 85%, 90%, 95%, 99%, or 100% Determine D or MCI). In another embodiment, this method determines at least about 40%, 45 %, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95 Determine the patient's brain injury (e.g., AD or MCI) with specificity of %, 99%, or 100%. The predetermined reference values ​​in these embodiments may be the cutoff values ​​shown in Table 22C. In yet another embodiment, the method has a sensitivity of at least 70% and at least 45% Specificity is used to determine the patient's brain injury (e.g., AD or MCI) based on IL-18 levels. In this embodiment, the predetermined reference value may be the cutoff value shown in Table 22C. In some cases, with a reference value of approximately 290 pg / mL, there is at least 70% sensitivity and at least It is also possible to achieve a specificity of 45%.

[0128] In one embodiment, MCI and AD in brain injury are compared using serum obtained from MCI patients versus AD patients. They can be distinguished by comparing the levels of IL-1β inside (for example, a predetermined reference value or (where is the range of the reference value). In some embodiments, the method is at least 70%, 75%, 8 Patient brain injury (e.g., A) with sensitivity of 0%, 85%, 90%, 95%, 99%, or 100% Determine D or MCI). In another embodiment, this method determines at least 40%, 45% 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% This determines the patient's brain injury (e.g., AD or MCI) with 99% or 100% specificity. The predetermined reference values ​​in these embodiments may be the cutoff values ​​shown in Table 22C. In another embodiment, the method provides at least 75% sensitivity and at least 40% characteristics The degree of IL-1β level is used to determine the patient's brain injury (e.g., AD or MCI). The predetermined reference value in this embodiment may be the cutoff value shown in Table 22C. In some cases, a reference value of approximately 0.46 pg / mL is used, with at least 75% sensitivity and at least... It is also possible to achieve a specificity of 40%.

[0129] In one embodiment, MCI and AD in brain injury are compared using serum obtained from MCI patients versus AD patients. They can be distinguished by comparing the levels of sAPPα within them (for example, a predetermined reference value or (where is the range of the reference value). In some embodiments, the method is at least 70%, 75%, 8 Patient brain injury (e.g., A) with sensitivity of 0%, 85%, 90%, 95%, 99%, or 100% Determine D or MCI). In another embodiment, this method determines at least 40%, 45% 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% This determines the patient's brain injury (e.g., AD or MCI) with 99% or 100% specificity. The predetermined reference values ​​in these embodiments may be the cutoff values ​​shown in Table 22C. In another embodiment, the method provides at least 70% sensitivity and at least 55% characteristics. The degree of abnormality determines the patient's brain injury (e.g., AD or MCI) based on the sAPPα level. The predetermined reference value in this embodiment may be the cutoff value shown in Table 22C. In some cases, with a reference value of approximately 8.84 ng / mL, there is at least 70% sensitivity and at least It is also possible to achieve a specificity of 55%.

[0130] In one embodiment, MCI and AD with brain injury are diagnosed using sAP in serum obtained from MCI patients. By comparing Pβ levels with those of AD patients (e.g., a given reference value or range of reference values), This can be used to distinguish them. In some embodiments, this method can be used to distinguish at least 60%, 65%, With sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% for patients To determine brain damage (e.g., AD or MCI). In another embodiment, this method is at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% , with specificity of 90%, 95%, 99%, or 100% for the patient's brain injury (e.g., AD or MCI). ) is determined. The predetermined reference values ​​for these embodiments are shown in Table 22C. It may be a value. In another embodiment, this method has a sensitivity of at least 60% and less With a specificity of at least 45%, based on the level of sAPPβ, the patient's brain injury (e.g., AD or Determine the MCI. The predetermined reference values ​​for this embodiment are the cuts shown in Table 22C. It may be an off value. In some cases, a reference value of approximately 0.63 ng / ml is less Both can achieve a sensitivity of 60% and a specificity of at least 45%.

[0131] In one embodiment, MCI and AD with brain injury were found in serum NFL obtained from MCI patients. The level is evaluated by comparing it with that of AD patients (e.g., a given reference value or range of reference values). It may be otherwise. In some embodiments, this method is used when the patient has brain injury (e.g., AD or MC). I) at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, The determination is made with a sensitivity of 99% or 100%. In another embodiment, this method is at least 40 %, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90 The diagnosis of a patient's brain injury (e.g., AD or MCI) is made with specificity of %, 95%, 99%, or 100%. The predetermined reference values ​​for these embodiments are the cutoff values ​​shown in Table 22C. It is possible. In another embodiment, this method has a sensitivity of at least 70% and at With a specificity of 40%, based on NFL levels, the patient's brain injury (e.g., AD or MCI) is diagnosed. Determine. The predetermined reference value for this embodiment is the cutoff value shown in Table 22C. It is possible. In some cases, a reference value of approximately 33.9 pg / ml is at least 70% This can achieve a sensitivity and a specificity of at least 40%.

[0132] In another embodiment, the disease, disorder, or condition associated with inflammation is an age-related disease. In terms of form, age-related disorders are controlled as provided herein (e.g., by a given reference). The elevation of ASC levels in the patient's serum compared to the range of values ​​or reference values. Detection with a sensitivity of at least 75%, 80%, 90%, 95%, 99%, or 100% AMD is such that the patient is determined to have AMD. In another embodiment, age-related disease The patient is a control as provided herein (e.g., a given reference value or range of reference values). Compared to the detection of elevated ASC levels in serum obtained from patients, Patient A AMD such that it is determined to have MD. Predetermined references to these embodiments The value may be the cutoff value shown in Table 29. In another embodiment, age-related diseases are , controls such as those provided herein (e.g., a given reference value or a range of reference values) By detecting elevated ASC levels in serum obtained from patients when compared, at least A patient is determined to have AMD with 90% sensitivity and at least 80% specificity. , AMD. The predetermined reference values ​​for this embodiment are the cutoff values ​​shown in Table 29. It is possible. In some cases, a reference value of approximately 365.6 pg / mL is at least It can achieve a sensitivity of 90% and a specificity of at least 85%.

[0133] In one embodiment, age-related diseases are controlled as provided herein (for example, Caspases in patient serum compared to a set reference value or range of reference values. -1 level increase detection indicates at least 60%, 65%, 70%, 75%, 80%, 9 A patient is determined to have AMD with a sensitivity of 0%, 95%, 99%, or 100%, AMD is an age-related disease. In another embodiment, age-related diseases are controlled as provided herein. When compared to a value (e.g., a predetermined reference value or range of reference values), serum obtained from a patient Detection of elevated caspase-1 levels in the body indicates at least 25%, 30%, 35%, and 40% %, 45%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85 The patient is determined to have AMD with specificity of %, 90%, 95%, 99%, or 100%. For example, AMD. The predetermined reference values ​​for these embodiments are shown in Table 29. It may be a set-off value. In another embodiment, age-related diseases are provided herein. When compared to a control (e.g., a specified reference value or range of reference values), the patient's The detection of elevated caspase-1 levels in the obtained serum indicates a sensitivity of at least 75% and This is AMD such that the patient is diagnosed with AMD with at least 30% specificity. The predetermined reference values ​​for this embodiment may be the cutoff values ​​shown in Table 29. In the case of tsuka, a reference value of approximately 6.136 pg / mL is sufficient for at least 75% sensitivity and It is possible to achieve a specificity of at least 30%.

[0134] In one embodiment, age-related diseases are controlled as provided herein (for example, IL-18 in patient serum compared to a set reference value or range of reference values. Detection of level increase indicates at least 70%, 75%, 80%, 90%, 95%, and 99% Alternatively, it is AMD such that the patient is determined to have AMD with 100% sensitivity. In this embodiment, age-related diseases are controlled by a control (e.g., a predetermined control) as provided herein. When compared to the reference value or range of reference values, the caspase levels in the serum obtained from patients are... Detecting a level increase of 1 indicates at least 45%, 50%, 55%, 60%, 65%, 7 Patients with specificity of 0%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% It is an AMD such that it is determined to have AMD. The illumination value may be the cutoff value shown in Table 29. In another embodiment, age-related diseases This refers to controls such as those provided herein (e.g., a given reference value or a range of reference values). In comparison, the detection of elevated IL-18 levels in serum obtained from patients indicates that there is less risk of [unclear]. The patient was determined to have AMD with at least 70% sensitivity and at least 50% specificity. This is an AMD that can be used. The predetermined reference values ​​for this embodiment are shown in Table 29. It may be a cutoff value. In some cases, a reference value of approximately 242.4 pg / mL is It can achieve a sensitivity of at least 70% and a specificity of at least 50%.

[0135] In one embodiment, age-related diseases are controlled as provided herein (for example, IL-1β in patient serum compared to a set reference value or range of reference values. Detection of a level increase indicates at least 45%, 50%, 55%, 60%, 65%, and 70% Patients have AMD with sensitivity of 75%, 80%, 90%, 95%, 99%, or 100%. AMD is such that it is determined that... In another embodiment, age-related disease is as described herein When compared to a control provided (e.g., a given reference value or range of reference values) By detecting elevated IL-1β levels in serum obtained from patients, at least 45% of cases were diagnosed. 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, AMD is a condition in which a patient is determined to have AMD with 99% or 100% specificity. There are. The predetermined reference values ​​for these embodiments are the cutoff values ​​shown in Table 29. In another embodiment, age-related diseases are controlled as provided herein. When compared to (for example, a predetermined reference value or range of reference values), the serum obtained from the patient Detection of elevated IL-1β levels provides at least 55% sensitivity and at least 50% characteristic This is an AMD such that the patient is determined to have AMD at a different degree. The predetermined reference value may be the cutoff value shown in Table 29. In some cases Therefore, a reference value of 0.842 pg / ml has a sensitivity of at least 55% and at least 50% Specificity can be achieved.

[0136] In another embodiment, the inflammation-related disease, disorder, or condition is non-alcoholic fatty liver disease. It is a type of NAFLD. In one embodiment, the type of NAFLD is as specified herein. When compared to controls provided by (e.g., a given reference value or range of reference values) In combination, detection of elevated ASC levels in serum obtained from patients indicates at least 75%, 8 The patient is determined to have NASH with a sensitivity of 0%, 90%, 95%, 99%, or 100%. NASH is a disease that is treated in a different embodiment. When compared to a control provided (e.g., a given reference value or range of reference values) The detection of elevated ASC levels in serum obtained from patients indicates that at least 65%, 7% Patients with specificity of 0%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% NASH is determined to have NASH. The predetermined reference value may be the cutoff value shown in Table 34. In another embodiment, the flame Diseases associated with the condition are controlled by the controls provided herein (e.g., a given reference value or The elevated levels of ASC in the patient's serum compared to the reference range. Based on the results, the patient has AMD with at least 80% sensitivity and at least 60% specificity. It is a NASH such that it is determined that... The predetermined reference values ​​for this embodiment are shown in the table The cutoff value can be 34. In some cases, it is approximately 394.9 pg / A reference value of mL can achieve at least 80% sensitivity and at least 60% specificity.

[0137] In one embodiment, inflammation-related diseases are controlled as provided herein ( For example, when compared to a predetermined reference value or range of reference values, the amount of I obtained from the patient's serum Detection of elevated L-18 levels indicates at least 60%, 65%, 70%, 75%, and 80% The patient was determined to have NASH with a sensitivity of 90%, 95%, 99%, or 100%. This is a type of NASH. In another embodiment, an inflammation-related disease is provided herein. When compared to a control that is used (for example, a predetermined reference value or range of reference values), Detection of elevated IL-18 levels in serum obtained from patients indicates at least 25%, 30% %, 35%, 40%, 45%, 45%, 50%, 55%, 60%, 65%, 70%, 75 Patients with NASH have specificity of %, 80%, 85%, 90%, 95%, 99%, or 100%. NASH such that it is determined to have. Predetermined references to these embodiments The value may be the cutoff value shown in Table 34. In another embodiment, the value is associated with inflammation. Diseases that are controlled by the control provided herein (e.g., a given reference value or reference value By detecting elevated IL-18 levels in serum obtained from patients compared to the normal range, The patient has NASH with at least 75% sensitivity and at least 60% specificity. This is a NASH such that it is determined to be NASH. The predetermined reference values ​​for this embodiment are shown in Table 34. The indicated cutoff value may be approximately 269.2 pg / ml. The reference value can achieve a sensitivity of at least 75% and a specificity of at least 60%. In any of the methods provided in this book, an inflammation-related disease, disorder, or condition (for example, Predicting or diagnosing NASH, MCI, AD, AMD, inflammatory aging, stroke, MS, or TBI The sensitivity and / or specificity of inflammasome proteins (e.g., ASCs) for blocking is, Determined by calculating the area under the curve (AUC) value along with a confidence interval (e.g., 95%). The area under the curve (AUC) is used along with the receiver operating characteristic (ROC) at 95% confidence interval. It can be determined from the curve.

[0138] In one embodiment, the disease, disorder, or condition associated with inflammation is brain injury. Brain injury is the same as at least one type of infrastructure in biological samples obtained from controls. Obtained from patients, the levels of masome proteins are elevated by a predetermined percentage, exceeding the normal level. The level or concentration of at least one inflammasome protein in the biological sample Detection indicates that the patient has MS. The obtained biological samples may be of the same type (e.g., serum or serum-derived EVs). The percentages are at most or at least about 50%, 55%, 60%, 65%, and 70%. %, 75%, 80%, 85%, 90%, 95%, 99%, 100%, 110%, 120% , 130%, 140%, 150%, 160%, 170%, 180%, 190%, or 200 It may be %. At least one inflammasome protein is caspase-1, IL -18, IL-1 beta, and ASC may be selected. ASC levels in serum samples obtained from the troll are at least 50% higher than those in the patient. The detection of ASC levels or concentrations in serum obtained from this indicates that the patient has MS. Yes, it is MS. In one embodiment, brain damage is known not to be AD. When compared to the levels of known MS biomarkers in samples obtained from rolls, patients Changes in the levels or concentrations of known MS biomarkers in samples obtained from the patient are also observed in the patient. When present, the ASC level is higher than that in the control sample from the patient. The detection of the level or concentration of ASC in the obtained sample indicates that the patient has MS. This is an MS (Mobile Suit) as shown.

[0139] In one embodiment, brain injury is the same in at least the same biological samples obtained from the control. It is also elevated by a certain percentage compared to the level of one type of inflammasome protein. , the detection of at least one inflammasome protein in biological samples obtained from patients A stroke is detected in such a way that the patient has a bell or concentration that it indicates the patient has a stroke. The biological samples obtained from the control may be of the same type (e.g., serum or blood). (EV derived from Qing). The specified percentages are at most or at least about 50%, 55%, 6%. 0%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, It may be 190% or 200%. At least one inflammasome protein is Spase-1, IL-18, IL-1 beta, and ASC may be selected. In one embodiment, Brain damage is less severe than ASC levels in serum samples obtained from controls. The detection of ASC levels or concentrations in serum obtained from patients is 70% higher, and the patient has had a stroke. A stroke is a condition that indicates the presence of a disease. In one embodiment, brain injury is a control At least 110% higher than the ASC levels in serum-derived EV samples obtained from rolls. The detection of the level or concentration of ASC in serum-derived EV obtained from the patient indicates that the patient has had a stroke. A stroke that indicates that the person is suffering from a stroke. In one embodiment, brain injury is a stroke Known strokes in samples obtained from controls known to be free of the disease When compared to the level of biomarkers, the known stroke in samples obtained from patients Changes in the level or concentration of intermediate biomarkers are also observed in patients, and these changes are obtained from the control group. ASC levels in patient-derived samples are higher than those in other samples. Alternatively, the detection of a concentration indicates that the patient has had a stroke.

[0140] In one embodiment, brain injury is the same in at least the same biological samples obtained from the control. It is also elevated by a certain percentage compared to the level of one type of inflammasome protein. , the detection of at least one inflammasome protein in biological samples obtained from patients The detection of a bell or concentration indicates that the patient has TBI. Biological samples obtained from controls may be of the same type (e.g., serum or blood). (EV derived from Qing). The specified percentages are at most or at least about 50%, 55%, 6%. 0%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, It may be 190% or 200%. At least one inflammasome protein is Spase-1, IL-18, IL-1 beta, and ASC may be selected. In one embodiment, Brain damage is less severe than ASC levels in serum samples obtained from controls. The detection of AS levels or concentrations in serum obtained from patients is 50% higher, and patients with TBI This is a TBI that demonstrates that... In one embodiment, brain injury is not a TBI... Known TBI biomarkers in samples obtained from known controls Compared to the known TBI biomarkers in patient samples, When the patient also has changes in level or concentration, in the serum sample obtained from the control Testing of ASC levels or concentrations in patient samples that are higher than the ASC level. The result is TBI, indicating that the patient has TBI.

[0141] In one embodiment, brain injury is the same in at least the same biological samples obtained from the control. It is also elevated by a certain percentage compared to the level of one type of inflammasome protein. , at least one inflammasome protein alone in a biological sample obtained from a patient or the level or concentration of the combination with at least one control biomarker protein. The detection of a certain degree indicates that the patient has MCI. Patient and control The biological samples obtained from the source may be of the same type (e.g., serum or serum-derived EVs). The specified percentages are at most or at least about 50%, 55%, 60%, and 65%. 70%, 75%, 80%, 85%, 90%, 95%, 99%, 100%, 110%, 1 20%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or It could be 200%. At least one inflammasome protein is caspase-1 , IL-18, IL-1 Beta and ASC may be selected. At least one controller Biomarker proteins are AB (1-42) , AB (1-40) sAPPα, It may be sAPPβ, T-Tau, or NFL. In one embodiment, brain injury is controlled ASC levels at least 50% higher than those in serum samples obtained from patients. The detection of AS levels or concentrations in the serum indicates that the patient has MCI. It is MCI. In one embodiment, brain injury is known not to be MCI. When compared to the levels of known MCI biomarkers in samples obtained from the patient, Changes in the level or concentration of known MCI biomarkers in samples obtained from individuals When a patient has it, the ASC level is higher than in the sample obtained from the control. The detection of ASC levels or concentrations in a sample obtained from the person indicates that the patient has MCI. This is an example of MCI (Mild Cognitive Impairment).

[0142] In one embodiment, brain injury is the same in at least the same biological samples obtained from the control. Also, one type of inflammasome protein and / or control biomarker protein In the biological samples obtained from patients, the level is elevated by a predetermined percentage above the specified level. At least one inflammasome protein alone or at least one control protein Detection of the level or concentration of a combination of Iomarker proteins indicates that the patient has AD. The AD is as shown. Biological samples obtained from patients and controls are of the same type. It may be (e.g., serum or serum-derived EVs). The given percentage is at most or At least approximately 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% %, 95%, 99%, 100%, 110%, 120%, 130%, 140%, 150%, It may be 160%, 170%, 180%, 190%, or 200%. At least one type The phramosome proteins include caspase-1, IL-18, IL-1 beta, and ASC. It can be selected from. At least one control biomarker protein is AB. ( 1-42) , AB (1-40) sAPPα, sAPPβ, T-Tau, or NFL Obtain. In one embodiment, brain injury is detected in serum samples obtained from controls. Testing of the level or concentration of AS in patient serum at least 50% higher than Bell's level. The result is AD, indicating that the patient has AD. In one embodiment, brain injury is A Known AD bios in samples obtained from controls known not to be D Compared to the level of the marker, the known AD bio in the patient samples When the patient also has changes in the level or concentration of the marker, the sample obtained from the control ASC level or concentration in patient samples that is higher than the ASC level in the sample. The detection of this indicates that the patient has AD.

[0143] In another embodiment, the disease, disorder, or condition associated with inflammation is an age-related disease. Morphologically, age-related diseases are the same in at least one biological sample obtained from a control. The level of inflammasome protein in the species is elevated by a certain percentage compared to the patient's level. Levels of at least one inflammasome protein in biological samples obtained from subjects Alternatively, the detection of a concentration indicates that the patient has AMD. Biological samples obtained from trolls may be of the same type (e.g., serum or serum-derived). EV). The specified percentages are at most or at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 100%, 110 %, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190 It may be % or 200%. At least one inflammasome protein is a casper protein. Ze-1, IL-18, IL-1β, and ASC may be selected. In one embodiment, aging The disease is at least 50% higher than the ASC level in serum samples obtained from the control group. If the detection of a high percentage of AS levels or concentrations in serum obtained from the patient indicates that the patient has AMD, This is an AMD that indicates the following: In one embodiment, it is a disease, disorder or condition related to inflammation. This refers to known AM in samples obtained from controls known to be lacking AMD. When compared to the levels of the D biomarker, known AMD in patient samples When the patient also has changes in the level or concentration of biomarkers obtained from the control, ASC levels in patient samples are higher than the ASC levels in the sample. The detection of the concentration indicates that the patient has AMD.

[0144] In one embodiment, a disease, disorder, or condition related to inflammation is obtained from a control. The same at least one inflammasome protein and / or controller in the body sample The patient's biomarker protein level is elevated by a certain percentage above the normal level. At least one inflammasome protein alone or in small numbers in the biological samples obtained Detection of the level or concentration of a combination with at least one control biomarker protein. However, the patient has NASH, indicating that the patient and the control... The biological samples obtained may be of the same type (e.g., serum or serum-derived EVs). The percentages are at most or at least about 50%, 55%, 60%, 65%, and 7%. 0%, 75%, 80%, 85%, 90%, 95%, 99%, 100%, 110%, 120 %, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or 20 It may be 0%. At least one inflammasome protein is IL-18 and AS It can be selected from C. At least one control biomarker protein is CR. It may be P(hs-CRP) or Gal-3. In one embodiment, for inflammation-related diseases, The disorder or condition is less severe than the ASC level in the serum sample obtained from the control. Both are 50% higher, and detection of ASC levels or concentrations in serum obtained from patients is possible if the patient is N It is NASH, which indicates that it is ASH. In one embodiment, it is an inflammation-related disease. The impairment or condition was obtained from a control known not to be NASH. Compared to the levels of known NASH biomarkers during the pull, the sample obtained from patients showed Known NASH biomarkers such as Gal-3 or CRP (hs-CRP) during the pull When the patient also has elevated levels or concentrations, AS in the sample obtained from the control The detection of ASC levels or concentrations in patient samples higher than level C is indicated by: The patient has NASH, indicating that they have NASH.

[0145] This invention relates to diseases, disorders, and other conditions caused by or associated with inflammation. Or the condition (e.g., MCI, AD, AMD, inflammatory aging, stroke, MS, or TBI) The method also provides a method for determining the prognosis for a patient. In one embodiment, this method is used to determine the prognosis for a patient. We provide the obtained biological samples and prepare the protein profiles described above. in a biological sample, at least one inflammasome protein alone or at least one This includes measuring the level of combination with one control biomarker protein, Inflammasome protein profile or control biomarker protein profile The prognosis of the patient is indicated by a predetermined reference value or reference value. Compared to one or more inflammasome proteins (e.g., IL-18, NLR) Elevated levels of P1, ASC, caspase-1, or a combination thereof indicate a worse prognosis. This indicates that one or more infrastructures are compared to a given reference value or a range of reference values. An increase of approximately 20% to 300% in somal protein levels indicates a worse prognosis. In some cases, the inflammasome protein is the ASC, and the given reference The values ​​may be derived from Tables 7-9, 16, 22A-C, or 23. In some embodiments, One or more control biomarker proteins compared to a fixed reference value or a range of reference values. Quality (for example, AB) (1-42) , AB (1-40) sAPPα, sAPPβ or A rise in the level of the NFL (or a combination thereof) indicates a worse prognosis. For example, One or more control biomarker proteins compared to a fixed reference value or a range of reference values. An increase of approximately 20% to 300% in the level of chloride indicates a worse prognosis. In the embodiment, one or more control units are compared with a predetermined reference value or a range of reference values. Omarker proteins (e.g., AB) (1-42) , AB (1-40) sAPPα, s An increase in the level of APPβ or NFL or a combination thereof, and one or more infrastructure Elevated somal proteins indicate a worse prognosis. For example, a given reference value or reference Approximately 2% of the levels of one or more control biomarker proteins compared to the range of values. An increase of 0% to approximately 300% and approximately 20% in the levels of one or more inflammasome proteins. An increase of approximately 300% indicates a worse prognosis.

[0146] In one embodiment, obtained from a patient in any of the diagnostic methods provided herein The expression of ASC levels in biological samples is known in the art and / or specified herein. Determined or detected through the use of any of the anti-ASC antibodies provided. In one embodiment In this specification, anti-ASC is a monoclonal antibody or a fragment thereof provided herein. Morphologically, anti-ASC antibodies are monoclonal antibodies that specifically bind to ASC, or antibodies that bind to ASC. This is a fragment, where this antibody or its antibody fragment has a heavy chain variable (VH) region and a light or cut region. It includes a variable (VL) region, and the amino acid sequence of the VH region is SEQ ID NO: 19 or SEQ ID NO: 19 It is at least 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of [the specified molecule]. It contains an amino acid sequence; the VL region amino acid sequence is SEQ ID NO: 30 or the amino acid sequence of SEQ ID NO: 30 Amino acids that are at least 95%, 96%, 97%, 98%, or 99% identical to the acid sequence. Includes sequence. In some cases, the VH region amino acid sequence and sequence number 19 are included. Monoclonal antibodies containing the VL region amino acid sequence including column number 30, or antibody cleavage derived therefrom. One of them could be called the IC-100.

[0147] Treatment method In one embodiment, inflammation or a disease caused by or related to inflammation, This is a method for treating patients who are suffering from or suspected of suffering from a disability or condition. Provided in the specification. Any method of treatment provided herein is caused by inflammation You have or are suspected of having a disease, disorder, or condition that is caused by or related to this disease, disorder, or condition. This may involve administering treatment to patients with a condition. In some cases, the methods provided herein Administration of treatment in a manner that can reduce inflammation in the patient. Reduction is controllable. This may be when compared to a group (for example, untreated patients and / or patients before treatment). In some cases, the treatment is a standard treatment procedure. In other cases, the treatment is a divine treatment. These are neuroprotective measures. Such neuroprotective measures reduce excitotoxicity, oxidative stress, and inflammation. It may contain drugs that alleviate the symptoms. Therefore, as an appropriate neuroprotective measure, methylprednisolone N, 17-alpha-estradiol, 17-beta-estradiol, ginsenoside , progesterone, simvastatin, deprenyl, minocycline, resveratrol and and other glutamate receptor antagonists (e.g., NMDA receptor antagonists) Antioxidants are, but are not limited to, antioxidants. In some embodiments, the treatment involves inframass Antibodies or their binding fragments directed against a protein, for example, provided herein. These include antibodies targeted against inflammasome proteins. In some cases Therefore, the treatment may be an extracellular vesicle (EV) uptake inhibitor. EV uptake inhibitors are It may be any EV reuptake inhibitor known in the art. In some cases, EV uptake inhibitors can be selected from those listed in Table 30. In some cases The treatment involves standard therapeutic procedures, neuroprotective measures, and treatments targeting inflammasome proteins. It is a combination of an antibody or a fragment derived therefrom and an EV uptake inhibitor.

[0148] In other embodiments, the person experiences inflammation or is caused by inflammation or A method for diagnosing or evaluating a patient with a related disease, disorder, or condition is, at least one of the above 1 Species inflammasome protein or at least one control biomarker protein Based on the measurement level of the protein, or inflammation or inflammation-induced or If a protein signature associated with a related disease, disorder, or condition is identified. , the aforementioned inflammation or any disease, disorder, or condition caused by or associated with inflammation This further includes administering treatment to the patient for inflammation or inflammation caused by inflammation. or related diseases, disorders or conditions (e.g., NASH, MCI, stroke, inflammatory bowel syndrome) Methods for diagnosing or evaluating patients as having aging, AMD, MS, AD, or TBI. This can be confirmed using the methods described herein. In some embodiments, inflammation is involved. A method for diagnosing or evaluating a patient having a related disease, disability, or condition is at least one of the above-mentioned types Based on the measurement levels of inflammasome proteins, or inflammation-related diseases and disorders Alternatively, a more severe disease, disorder, or condition associated with the condition or inflammation and the associated protein If a signature is identified, this further includes providing treatment to the patient. In some cases, the treatment is a standard treatment procedure. In some cases, the treatment is neuroprotective. This is a treatment. In some cases, the treatment is an inflammasome provided herein. Antibodies directed against proteins, such as antibodies directed against inflammasome proteins. It is an antibody or its conjugated fragment. In some cases, the treatment involves extracellular vesicles (EVs). It may be an EV reuptake inhibitor. An EV reuptake inhibitor is any EV known in the art. It may be an uptake inhibitor. In some cases, EV uptake inhibitors are shown in Table 30. It can be selected from what is observed. In some cases, the procedure is standard treatment, nerve Protective measures, antibodies or fragments derived therefrom directed against inflammasome proteins and A combination of either an EV uptake inhibitor or a combination of the above. In some cases, as specified herein The administration of treatment in the manner provided may reduce inflammation in the patient. This may be in comparison to a control group (e.g., untreated patients and / or patients before treatment). ru.

[0149] Treatment of inflammation or diseases, disorders, or conditions caused by or associated with inflammation. Regarding any of the methods of the treatment embodiments provided herein for placing inflammation, It could be inflammation of the natural immune system. The inflammation could be inflammasome-related inflammation. Disease, disorder or The conditions include brain injury, age-related diseases, inflammatory aging, autoimmunity, autoinflammation, metabolic or neurodegenerative disorders. A group consisting of diseases may be selected. In some cases, a disease, disorder, or condition is a flammation. It is symptomatic aging. In some cases, the disease, disorder, or condition is NASH. In some cases, the age-related disease is age-related macular degeneration (AMD). In this context, the disease, disability, or condition is brain injury. Brain injury is a type of traumatic brain injury (TBI). The group may be selected from those consisting of stroke and spinal cord injury (SCI). Autoimmune or neurodegenerative diseases. This includes amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease (PD), and muscular dystrophy. Strophy (MD), immune dysfunction muscle CNS collapse, systemic lupus erythematosus, lupus nephritis, joints Rheumatism, inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis), and multiple sclerosis (MS) ) can be selected from. Metabolic diseases include metabolic syndrome, obesity, diabetes, and diabetes. Diabetic nephropathy or diabetic kidney disease (DKD), insulin resistance, atherosclerosis, lipid Glycogen storage disorders, glycogen storage disorders, medium-chain acyl-coenzyme A dehydrogenase deficiency , non-alcoholic fatty liver disease (e.g., non-alcoholic steatohepatitis (NASH)) and gout It can be selected from the following. Autoinflammatory diseases include cryopyrin-associated periodic syndromes (CAPS). CAPS is a familial cold autoinflammatory syndrome (FCAS), also known as Mackle-Wells disease. This may include multiple inflammatory bowel syndromes (MWS) and neonatal-onset multi-system inflammatory diseases (NOMID).

[0150] In one embodiment, brain injury (e.g., AD, MCI, TBI, stroke, or MS) is treated with MS. Yes, standard treatment procedures may alter the disease outcome, manage recurrence, manage symptoms, or either change the disease outcome. A selection of treatments for those combinations. Treatments for altering disease outcomes. These include beta-interferon, glatiramer acetate, fingolimod, and teriflunomide. dimethyl fumarate, mitoxantrone, ocrelizumab, alemtuzumab, dacrizuma The choice may be between bu and natalizumab. Stroke can be ischemic stroke, transient ischemic stroke or This could be a hemorrhagic stroke.

[0151] In another embodiment, brain injury (e.g., AD, MCI, TBI, stroke, or MS) is ischemia This is a transient ischemic stroke or transient ischemic stroke, and the standard treatment is tissue plasminogen activation. Factor (tPA), antiplatelet drugs, anticoagulants, carotid angioplasty, carotid endarterectomy, cerebral ischemia Select from intra-arterial thrombolysis and mechanical clot removal (MERCI) or a combination thereof. In yet another embodiment, brain injury (e.g., TBI, stroke, or MS) is hemorrhagic. The patient has a stroke, and the standard treatment is aneurysm clipping, coil embolization, or arteriovenous malformation (A). VM) Repair.

[0152] In another embodiment, brain injury (e.g., AD, MCI, TBI, stroke, or MS) is TB I, and standard treatments include diuretics, antiepileptic drugs, coma inducers, surgery and / or These are selected from rehabilitation. Diuretics reduce the amount of fluid in the tissues and increase urine excretion. It can be used to increase excretion. Diuretics administered intravenously to patients with traumatic brain injury. This may promote a decrease in internal brain pressure. Antiepileptic drugs are used to treat epileptic seizures. It may be given during the first week to avoid any further brain damage that could occur. Antiepileptic seizure treatment is used only when an epileptic seizure occurs. Coma-inducing drugs are used. Because the brain in a coma requires less oxygen to function, a person enters a transient coma. It may be a drug used to do this. This is because blood vessels are compressed due to increased intracranial pressure. This may be particularly beneficial in cases where brain cells cannot receive a normal amount of nutrients and oxygen. (Severe TBI) The degree can be assessed using the Glasgow Coma Scale. This 15-point test is administered by a physician or other Emergency medical personnel check a person's ability to move their eyes and limbs according to instructions. This can facilitate the assessment of the initial severity of brain damage. Speech integration is also an important factor. It may provide assistance. Ability is scored on a scale of 3 to 15 using the Glasgow Coma Scale. A higher core value indicates a lower severity of damage.

[0153] In another embodiment, brain injury (e.g., AD, MCI, TBI, stroke, or MS) is M Computerized cognitive training (CI) and standard treatment procedures include computerized cognitive training, group memory training, and individual error-free learning. Session, Family Memory Strategy intervention, DHA (docosahexaenoic acid), E PA (eicosapentaenoic acid), Ginkgo biloba, Donepe Jill, Rivastigmin, Triflusar, Huannao Yi cong) capsules, pyribezil, nicotine patch, vitamin E, vitamin B12 and B12 6. Folic acid, rofecoxib, galantamine, cholinesterase inhibitor memantine, lith Um, Wuzi Yanzong granules, ginseng and exercise It will be selected.

[0154] In another embodiment, brain injury (e.g., AD, MCI, TBI, stroke, or MS) is A D is the standard treatment, and the standard treatment is computerized cognitive training, group memory training, and individual error-free learning. Medications, Family Memory Strategy intervention, DHA (docosahexaenoic acid), EP A (eicosapentaenoic acid), Ginkgo biloba, Donepez Lu, Rivastigmin, Triflusar, Huannao Yic (ong) Capsules, Pyribezil, Nicotine Patch, Vitamin E, Vitamin B12 & B6, Folic acid, rofecoxib, galantamine, cholinesterase inhibitor memantine, lithium Select from Wuzi Yanzong granules, ginseng, and exercise. The standard treatment involves cholinesterase inhibitors and memantine (Namenda). Cholinesterase inhibitors include donepezil (Aricept) and galantamine. (Lazadyne) and rivastigmine (Exelon) may be selected.

[0155] In one embodiment, the autoimmune disease is rheumatoid arthritis (RA), and the standard treatment is nonsteroidal anti-inflammatory drugs (NSAIDs). Drugs (NSAIDs), steroids (e.g., prednisone), disease-modifying antirheumatic drugs (DM) ARDs and biological agents can be selected. NSAIDs include ibuprofen (ARDs). Examples include Dovil (Motrin IB) and naproxen sodium (Aleve). MARDs include methotrexate (Trexall, Otrexup, etc.) and Lefulno. Mid (Arava), hydroxychloroquine (Plaquenil), and sulfasalazine (Aza) Rufidine is one example. As for biological agents, abatacept (Orencia), Darimumab (Humira), Anakinra (Kineret), Baricitinib (Olumiento), Certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi) ), infliximab (Remicade), rituximab (Rituxan), sarilumab (Keb) Examples include Zara, tocilizumab (Actemra), and tofacitinib (Xeljanz). .

[0156] In one embodiment, the autoimmune disease is lupus nephritis, and the standard treatment is to regulate blood pressure. Examples include medications and / or special diets low in protein and salt. Furthermore, Standard treatment for lupus nephritis includes, for example, nonsteroidal anti-inflammatory drugs (NSAIDs) and antimalarial drugs. Drugs, corticosteroids (e.g., prednisone; methylprednisolone), immunosuppressants or This could be a treatment for lupus, such as biological agents. An example of an NSAID is naproxen. Examples include sen sodium (Aleve) and ibuprofen (Advil, Motrin IB, etc.). It is possible. An example of an antimalarial drug could be hydroxychloroquine (Plaquenil). Immunity Examples of inhibitors include azathioprine (Imuran, Azasan) and mycophenolate mo Examples include fethyl (CellCept) and methotrexate (Trexall). Examples of formulations include belimumab (Benlysta) or rituximab (Rituxan). It is possible.

[0157] In one embodiment, the metabolic disease is NASH, and the standard treatment is weight loss, etc. Lifestyle changes, increased exercise, avoidance of liver-damaging drugs, and lower cholesterol. Management of diabetes may also be mentioned. NASH is non-alcoholic fatty liver disease (NASH). This is a type of AFLD. NAFLD refers to people who drink little or no alcohol. NAFLD is a general term for a range of liver conditions that affect the liver cells. The main characteristic of NAFLD is the liver cells. This is characterized by excessive fat storage in the liver, inflammation of the liver, and scarring and irreversible damage. It can progress to this stage. This injury may be similar to the injury caused by heavy drinking. In its most severe forms, non-alcoholic steatohepatitis can progress to cirrhosis and liver failure. ru.

[0158] In one embodiment, the metabolic disease is diabetic neuropathy, and the standard treatment is Lifestyle changes such as weight loss, increased exercise, lower cholesterol, and protein in urine Examples include quality control, promotion of bone health, regulation of hypertension, management of diabetes, and kidney dialysis or transplantation. Diabetic nephropathy, also known as diabetic kidney disease (DKD), is a condition affecting type 1 diabetes and type 2 diabetes. This is a severe kidney-related complication of a urinary tract disease.

[0159] In one embodiment, the autoimmune disease is IBD, and the standard treatment is anti-inflammatory drugs, immunotherapy. Epidemic suppressants, antibiotics, antidiarrheals, analgesics, iron supplements and calcium and vitamins One possible example is the N-D supplement. As for antibiotics, ciprofloxacin (Cipro) and Metronidazole (Flagyl) is one example. An example of an immunosuppressant is azathioprine. Purine (Azasan, Imran), Mercaptopurine (Purinethol, Pur ixan), cyclosporine (Gengraf, Neoral, Sandimmune) and methotrexate Trexal is one example. Other examples of immunosuppressants include tumor necrosis. Death factor (TNF)-alpha inhibitors or biologics, such as infliximab (Remicade) ), adalimumab (Humira), golimumab (Simponi), natalizumab (Tysabri) Examples include vedolizumab (Entyvio) and ustekinumab (Stelara). As anti-inflammatory agents, corticosteroids and aminosalicylic acids, such as mesalamine ( Asacol HD, Delzicol), balsalazide (Colazar) and olsalazine ( IBD (Dipentum) is one example. IBD describes disorders involving chronic inflammation of the gastrointestinal tract of an individual. This is a general term used to describe IBD. Examples of IBD include ulcerative colitis and Crohn's disease. It is possible. Ulcerative colitis is a persistent lining of the innermost layer of the human large intestine (colon) and rectum. While ulcers are inflammation and pain in the digestive tract, Crohn's disease is characterized by inflammation of the lining of the digestive tract. This often spreads deep into the affected tissue.

[0160] In one embodiment, the autoinflammatory disease is CAPS, and the standard treatment is intervention. Leukin-1-targeted biological agents and adjuvant therapies for treating joint deformities. Nonsteroidal anti-inflammatory drugs, corticosteroids, or methamphetamine to alleviate symptoms and irritation. Trexate is one example. Cryopyrin-associated autoinflammatory syndrome is also known as cryopyrin Phosphorus-related periodic syndromes (CAPS) are associated with deletions of the same gene (i.e., NLRP3). Three autoinflammatory diseases: neonatal-onset multiorgan inflammatory disease (NOMID), Mackle disease. It consists of Wells syndrome (MWS) and familial cold autoinflammatory syndrome (FCAS). NO MID is characterized by fever accompanied by inflammation in multiple organs. The initial symptoms of NOMID include itching. Hives-like rash; inflammation of the membranes surrounding the brain causing headache, blindness or hearing loss; and eye ailments. A bloated appearance; and possibly episodes of vomiting. After 1 year of age, half of children with NOMID are involved. Joint pain and swelling may develop. MWS is a severe form of the disease accompanied by skin rash, conjunctivitis, joint pain, and vomiting. It is characterized by intermittent symptoms, including severe headaches. Episodes last 1 to 3 days. Complete hearing loss often occurs by the teenage years. FCAS is characterized by fever, chills, and vomiting. It is characterized by nausea, extreme thirst, headache, and joint pain.

[0161] In one embodiment, the present invention relates to inflammation or inflammation in the subject This refers to a method for treating a disease, disorder, or condition related thereto, which involves antibodies or those Intended use of an active fragment, the antibody or its active fragment is a mammalian inflammasome or In another embodiment, the antigen or epitope component from which the administration is to be performed The drugs are antisense RNA or siRs that target the components of the mammalian inflammasome. It is NA. Inflammasome components include, for example, NAPL1, NALP2, and NALP3. , NLRC4 or AIM2 inflammasome, or any other inflammasome known in the art It may be a component of the ramosome. In a typical embodiment, this antibody is an ASC or antigen Or it specifically binds to epitopes derived therefrom. However, mammalian inflammasomes (e.g.) For example, NALP1, NALP2, NALP3, NLRC4, or AIM2 inflammasomes. Antibodies against any other component of ) may be used.

[0162] Antibodies as described herein include monoclonal or polyclonal antibodies or their activity It may be a fragment. The antibody or active fragment may be a chimeric, human or hi as described herein. It could be a transformation.

[0163] In one embodiment, the antibody or its active fragment is used with mammalian inflammasomes (e.g., AI). Specific to at least one component (e.g., ASC, AIM2) of the M2 inflammasome. Targeted binding, components or antigens of mammalian inflammasomes or epithelial cells derived therefrom. For use in the methods described herein, components of mammalian inflammasomes The representative antibodies in question are incorporated herein by reference in their entirety. This may be as described in U.S. Patent No. 8,685,400. In one embodiment, The antibodies or antibody fragments provided in this specification are incorporated herein by reference in whole. In mammals as described in U.S. Patent No. 8,685,400 It may be used in methods for reducing inflammation. Antibodies or so in methods for treating inflammation The use of these antibody fragments may reduce inflammation. The use of antibodies or their antibody fragments (inflammation) In the methods for treatment, innate immunity or inflammasome-associated inflammation in the patient This can reduce the risk. The reduction is achieved in the control group (e.g., untreated patients and / or patients before treatment) and This may be the case when comparing. In one embodiment, the antibody or antibody fragment derived therefrom causes inflammation or To treat diseases, disorders, or conditions caused by or associated with inflammation. It is used for this purpose. Inflammation can be innate immune inflammation. Inflammation is related to the inflammasome mechanism. It may be a inflammatory condition. Diseases, disorders, or conditions include brain injury, age-related diseases, inflammatory aging, and autoimmune diseases. The group may be selected from autoinflammatory, metabolic, or neurodegenerative diseases. In some cases, age-related diseases are inflammatory aging. This is age-related macular degeneration (AMD). In some cases, the disease, disorder, or condition affects the brain. Brain injury is a type of injury. Brain injury can range from traumatic brain injury (TBI), stroke, and spinal cord injury (SCI). They can be selected from the following groups. Autoimmune or neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease (PD), muscular dystrophy (MD), immune deficiency Muscle CNS breakdown, systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, inflammatory bowel disease (e.g., chlorosis) It can be selected from disease (including ulcerative colitis) and multiple sclerosis (MS). Metabolic diseases are, Metabolic syndrome, obesity, diabetes, diabetic nephropathy, or diabetic kidney disease (DKD) Insulin resistance, atherosclerosis, lipid storage disorders, glycogen storage disorders, Medium-chain acyl-coenzyme A dehydrogenase deficiency, non-alcoholic fatty liver disease (e.g.) Autoinflammatory diseases may be selected from non-alcoholic steatohepatitis (NASH) and gout. This could be cryopyrin-associated periodic syndrome (CAPS). CAPS is a familial cold-associated syndrome. Facial inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal onset multifocal disease. This may include organ system inflammatory diseases (NOMIDs). Antibodies or antibody fragments derived therefrom are monoclonal. This antibody may be a ronal antibody or may be derived from a monoclonal antibody. The antibody fragment may be a polyclonal antibody or may be derived from a polyclonal antibody. The antibody fragments are Fab, F(ab')2, Fab', scFv, single-domain antibody, and dia. This could be a body or single-chain camel antibody. This antibody or an antibody fragment derived therefrom (e.g., monoclonal). The antibody (or its antibody fragment) may be human, humanized, or chimeric.

[0164] In one embodiment, the antibody or antibody fragment derived therefrom is used by individuals who are suffering from MS or are not suffering from MS In patients suspected of having MS, administering this antibody or antibody fragments derived therefrom can treat the condition. Used for placement. In some cases, administration of this antibody or its antibody fragments. This reduces the level of inflammatory cytokines, at least. As a result of administration, inhibition of inflammasome activation may occur in the subjects. In some cases In some cases, this antibody or its antibody fragment may be effective against ASC. In this case, when administered with this antibody or its antibody fragment, the ASC was compared to the control. A decrease in activity occurs. Controls may be untreated subjects. Administration is intraventricular and peritoneal. It may be administered internally, intravenously, or by inhalation. This antibody or antibody fragments derived therefrom are monochromatic. It may be a monoclonal antibody or may be derived from a monoclonal antibody. This antibody or derived from it The antibody fragment may be a polyclonal antibody or may be derived from a polyclonal antibody. This antibody fragment is Fab, F(ab')2, Fab', scFv, single-domain antibody, dia It may be a body or single-chain camel antibody. This antibody or an antibody fragment derived therefrom (e.g., monoclonal) The ronal antibody (or its antibody fragment) may be human, humanized, or chimeric.

[0165] In one embodiment, the antibody or antibody fragment derived therefrom is used to describe a person who is PD or is not PD. By administering this antibody or antibody fragments derived therefrom to patients suspected of having PD, the disease can be treated. Used for placement. In some cases, administration of this antibody or its antibody fragments. This reduces the level of inflammatory cytokines, at least. As a result of administration, inhibition of inflammasome activation in the target may occur. In some cases In some cases, this antibody or its antibody fragment may be effective against ASC. In this case, when the administration of this antibody or its antibody fragment was compared with the control, ASC Decreased activity occurs. Controls may be untreated subjects. Administration is intraventricular and intraperitoneal. This may be administered intravenously or by inhalation. This antibody or antibody fragment derived therefrom is monoclonal. It may be a monoclonal antibody or may be derived from a monoclonal antibody. This antibody or an antibody derived therefrom The body fragment may be a polyclonal antibody or may be derived from a polyclonal antibody. Antibody fragments include Fab, F(ab')2, Fab', scFv, single-domain antibody, and diabolic antibody. This may be a di or single-chain camel antibody. This antibody or an antibody fragment derived therefrom (e.g., monoclonal The antibody (or its antibody fragment) may be human, humanized, or chimeric.

[0166] In one embodiment, the antibody or antibody fragment derived therefrom is used to describe a person who is suffering from lupus nephritis or is suffering from lupus nephritis. By administering this antibody or antibody fragments derived therefrom to patients suspected of having lupus, It is used to treat nephritis. In some cases, this antibody or its antibody fragments Administration of this antibody reduces the level of inflammatory cytokines at least. The administration of one of these substances may result in inhibition of inflammasome activation in the target. In some cases, this antibody or its antibody fragments may be effective against ASC. In that case, if the results of administering this antibody or its antibody fragment are compared to the control A decrease in ASC activity occurs. The control group may be untreated. Administration is performed in the ventricles. It may be administered internally, intraperitoneally, intravenously, or by inhalation. This antibody or antibody fragments derived therefrom are It may be a monoclonal antibody or may be derived from a monoclonal antibody. This antibody or so The antibody fragment derived from this may be a polyclonal antibody or may be derived from a polyclonal antibody. This antibody fragment is Fab, F(ab')2, Fab', scFv, a single-domain antibody. This could be a diabody or single-chain camel antibody. This antibody or antibody fragment derived therefrom (for example) Monoclonal antibodies (or their antibody fragments) may be human, humanized, or chimeric.

[0167] In one embodiment, the antibody or antibody fragment derived therefrom is used by individuals suffering from diabetic nephropathy or This involves administering this antibody or antibody fragments derived therefrom to patients suspected of having the disease. It is used to treat diabetic nephropathy. In some cases, this antibody or its anti- Administration of the body fragment reduces the level of inflammatory cytokines at least. This antibody or Administration of the antibody fragment may result in inhibition of inflammasome activation in the target. In some cases, this antibody or its antibody fragment may be effective against ASC. In some cases, the results of administering this antibody or its antibody fragments were compared to the control. In this case, ASC activity decreases. Controls may be untreated subjects. Administration is to the ventricles. It may be administered internally, intraperitoneally, intravenously, or by inhalation. This antibody or antibody fragments derived therefrom are It may be a monoclonal antibody or may be derived from a monoclonal antibody. This antibody or so The antibody fragment derived from this may be a polyclonal antibody or may be derived from a polyclonal antibody. This antibody fragment is Fab, F(ab')2, Fab', scFv, a single-domain antibody. This could be a diabody or single-chain camel antibody. This antibody or antibody fragment derived therefrom (for example) Monoclonal antibodies (or fragments thereof) may be human, humanized, or chimeric.

[0168] In one embodiment, the antibody or antibody fragment derived therefrom is used by a person suffering from NASH or By administering this antibody or antibody fragments derived therefrom to patients suspected of having the disease, NA Used to treat SH. In some cases, this antibody or its antibody fragments Administration of this antibody reduces the level of inflammatory cytokines at least. The administration of one of these substances may result in inhibition of inflammasome activation in the target. In some cases, this antibody or its antibody fragment may be effective against ASC. In some cases, when the administration of this antibody or its antibody fragment is compared to the control, A SC activity decreases. Controls may be untreated subjects. Administration is intraventricular and intraperitoneal. It may be administered internally, intravenously, or by inhalation. This antibody or antibody fragment derived therefrom is monoclonal. This antibody may be a ronal antibody or may be derived from a monoclonal antibody. The antibody fragment may be a polyclonal antibody or may be derived from a polyclonal antibody. This antibody fragment is Fab, F(ab')2, Fab', scFv, single-domain antibody, dye This antibody may be an abodi or single-chain camel antibody. This antibody or an antibody fragment derived therefrom (e.g., monoclonal) The ronal antibody (or its antibody fragment) may be human, humanized, or chimeric.

[0169] In one embodiment, the antibody or antibody fragment derived therefrom is infected with CAPS or infected By administering this antibody or antibody fragments derived therefrom to patients suspected of having CA Used to treat PS. In some cases, this antibody or its antibody sterilization Administration of this antibody or those Administration of the antibody fragment may result in inhibition of inflammasome activation in the target. In some cases, this antibody or its antibody fragment may be effective against ASC. In some cases, the results of administering this antibody or its antibody fragments were compared to the control. In this case, ASC activity decreases. Controls may be untreated subjects. Administration is to the ventricles. It may be administered internally, intraperitoneally, intravenously, or by inhalation. This antibody or antibody fragments derived therefrom are It may be a monoclonal antibody or may be derived from a monoclonal antibody. This antibody or so The antibody fragment derived from this may be a polyclonal antibody or may be derived from a polyclonal antibody. This antibody fragment is Fab, F(ab')2, Fab', scFv, a single-domain antibody. This could be a diabody or single-chain camel antibody. This antibody or antibody fragment derived therefrom (for example) Monoclonal antibodies (or their antibody fragments) may be human, humanized, or chimeric.

[0170] In one embodiment, the antibody or antibody fragment derived therefrom is used by a person suffering from AMD or other related conditions. By administering this antibody or antibody fragments derived therefrom to patients suspected of having AMD, It is used to treat [condition]. In some cases, the administration of this antibody or its antibody fragments. This reduces the level of inflammatory cytokines, at least. As a result of administration, inhibition of inflammasome activation in the target may occur. In some cases In this context, this antibody or its antibody fragments may be effective against ASC. In some cases, when the administration of this antibody or its antibody fragment is compared to the control, A SC activity decreases. Controls may be untreated subjects. Administration is intraventricular and intraperitoneal. It may be administered internally, intravenously, or by inhalation. This antibody or antibody fragments derived therefrom are monochromatic. It may be a monoclonal antibody or may be derived from a monoclonal antibody. This antibody or derived from it The antibody fragment may be a polyclonal antibody or may be derived from a polyclonal antibody. This antibody fragment is Fab, F(ab')2, Fab', scFv, single-domain antibody, dia This could be a body or single-chain camel antibody. This antibody or an antibody fragment derived therefrom (e.g., monoclonal). The antibody (or its fragments) may be human, humanized, or chimeric.

[0171] In one embodiment, the antibody or antibody fragment derived therefrom is used to treat inflammatory aging or age-related inflammation. Administer this antibody or antibody fragments derived therefrom to patients who are infected or suspected of being infected. It is used to treat inflammatory aging or age-related inflammation in some cases. In this case, administration of this antibody or its antibody fragments increases the level of inflammatory cytokines at least. Inflammasome activity in the target group decreases as a result of administration of this antibody or its antibody fragment. Inhibition of the compound may occur. In some cases, this antibody or its antibody fragments may affect ASC. It may be the opposite. In some cases, as a result of administering this antibody or its fragments, Compared to the control group, ASC activity is reduced. The control group is the untreated group. This may be the case. Administration may be by intraventricular, intraperitoneal, intravenous, or inhalation. This antibody or The antibody fragment derived therefrom may be a monoclonal antibody or derived from a monoclonal antibody. This antibody or antibody fragments derived therefrom may be polyclonal antibodies or It may be derived from a liclonal antibody. This antibody fragment is Fab, F(ab')2, Fab', This antibody may be scFv, a single-domain antibody, a diabody, or a single-chain camel antibody. Antibody fragments derived from this (e.g., monoclonal antibodies or their antibody fragments) are human, humanized or It could be a chimera.

[0172] The antibody or antibody fragment of this embodiment is a pharmaceutical composition such as, for example, one provided herein. Substances such as substances may be present in the composition. This composition contains at least one pharmaceutically acceptable carrier. or may further include a diluent. In one embodiment, inflammation or inflammation-induced or The methods provided herein for treating disorders, diseases, or conditions related thereto , a low amount of therapeutically effective mammalian inflammasomes (e.g., AIM2 inflammasomes) The following are provided herein that specifically bind to at least one component (e.g., ASC):...

Claims

1. A method for evaluating a patient suspected of having mild cognitive impairment (MCI), wherein the patient The expression level of at least one inflammasome protein in the biological samples obtained Measuring the bell and the at least one inflammaso in the biological sample The expression level of the protein is determined by the expression level of one or more control MCI biomarkers. To compare with Bell, and the at least one inflammaso in the biological sample. The expression level of the mu protein is in front of one or more control MCI biomarkers. This includes selecting the patient as having MCI if the symptom level is similar to the one described above. A way to do it.

2. The expression level of at least one inflammasome protein or the expression level The parameter representing the expression of one or more control MCI biomarkers Level or parameter representing the expression level: 10%, 9%, 8%, 7%, 6%, 5% , if within 4%, 3%, 2%, or 1%, then at least one type of inflammasome The expression level of the protein is the same as that of one or more control MCI biomarkers. The method according to claim 1, which is similar to the expression level.

3. The expression level of the one or more control MCI biomarkers is from the patient The method according to claim 1, wherein the measurement is performed in the obtained biological sample.

4. The expression levels of the one or more control MCI biomarkers previously indicated MCI The method according to claim 1, measured in a biological sample obtained from an individual diagnosed with the condition. 。

5. The biological samples obtained from individuals previously diagnosed with MCI are affected by MCI. This is the same type of biological sample obtained from the aforementioned patient suspected of having the disease. The method according to claim 4.

6. The expression level of at least one inflammasome protein and one or more of the above. The expression levels of the control MCI biomarkers are obtained from the control. The expression level of at least one inflammasome protein in a physical sample and The expression level of one or more control MCI biomarkers is enhanced. The method according to claim 1.

7. The biological sample obtained from the control is from a suspected case of MCI. A biological sample of the same type as that obtained from a certain patient, as described in claim 6. method.

8. The aforementioned control is a healthy individual, and the healthy individual exhibits clinical symptoms consistent with MCI. The method according to claim 6, wherein the individual does not exhibit the characteristic.

9. The expression level of at least one inflammasome protein and one or more of the above. The expression level of the control MCI biomarker is the expression level of at least one of the inf Regarding ramasomal proteins and the one or more control MCI biomarkers The method according to claim 1, wherein the value is augmented with respect to a predetermined reference value or range of reference values.

10. A parameter representing the expression level of at least one inflammasome protein. - and the parameter representing the expression level of the one or more control MCI biomarkers The method according to claim 6, wherein the vector is the area under the curve (AUC).

11. The method according to claim 1, wherein the patient exhibits clinical symptoms consistent with MCI.

12. The biological samples obtained from the patient suspected of having MCI were found to be cerebral vertebrae. Cerebrospinal fluid (CSF), CNS microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (E V) The method according to claim 1.

13. The at least one inflammasome protein and / or the one or more controllers The expression level of the MCI biomarker is the expression level of the at least one inflammasome Directed toward proteins and / or one or more control MCI biomarkers The method according to claim 1, which is measured by an immunoassay using one or more antibodies. Law.

14. The aforementioned at least one inflammasome protein is interleukin 18 (IL- 18) Apoptosis-related specular type containing IL-1β caspase recruitment domain The method according to claim 1, wherein the protein (ASC), caspase-1, or a combination thereof. 。

15. The claim according to claim 1, comprising at least one inflammasome protein ASC. The method.

16. The at least one inflammasome protein comprises IL-18, according to claim 1. Method of description.

17. The one or more control MCI biomarkers mentioned above are neurofilament light markers. Lipeptides (NFL), soluble APP-alpha (sapα) and / or soluble APP- The method according to claim 1, wherein the molecule is beta (sAPPβ).

18. The at least one inflammasome protein is an ASC, and the one or more The control MCI biomarker above is soluble APP-alpha (sAPPα). The AUC of ASC is 0.974, and the AUC of sAPP-alpha is The method according to claim 10, wherein the coefficient is 0.9687.

19. The at least one inflammasome protein is an ASC, and the one or more The control MCI biomarker shown above is soluble APP-beta (sAPPβ). The AUC of ASC is 0.974, and the AUC of sAPP-beta is 0 The method according to claim 10, wherein the result is 9068.

20. The at least one inflammasome protein is an ASC, and the one or more The control MCI biomarker above is neurofilament light polypeptide ( NFL) and the AUC of ASC is 0.974, and the AUC of NFL is The method according to claim 10, wherein the coefficient is 0.7734.

21. The biological sample obtained from the patient is serum, and the patient is less Sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% The method according to claim 1, selected as having MCI with a specificity of at least 55%.

22. The biological sample obtained from the patient is serum, and the patient is less With sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100%, M The method according to claim 1, selected as having CI.

23. The biological sample obtained from the patient is serum, and the patient is less Both are selected as having MCI with a sensitivity of 70% and a specificity of at least 55%. The method described in item 1.

24. The aforementioned specificity and / or sensitivity are determined using a receiver operating characteristic (ROC) curve with a 95% confidence interval. The method according to claim 21, which is determined by the method described.

25. To select the patient as having MCI, one or more symptoms associated with MCI The method according to claim 1, further comprising evaluating the existence of.

26. One or more of the above symptoms associated with MCI include amnesia, lack of concentration, anxiety, indecisiveness, and difficulty directing. Difficulty solving problems, difficulty planning, difficulty moving in unfamiliar environments, impulsive or questionable judgments, and complex tasks or visual impairments. A determination of the time or sequence of steps required to complete perception, as described in claim 25. method.

27. A method for evaluating a patient suspected of having Alzheimer's disease (AD), the patient Expression of at least one inflammasome protein in biological samples obtained from Measuring the level and the at least one inframa in the biological sample The expression level of the aforementioned protein is determined by the expression level of one or more control AD ​​biomarkers. To compare with Bell, and the at least one inflammaso in the biological sample. The expression level of the protein is the same as that of one or more control AD ​​biomarkers. A method that includes selecting the patient as having AD if the expression levels are similar. Law.

28. The expression level of at least one inflammasome protein or the expression level The parameter representing the expression level of the one or more control AD ​​biomarkers Bell or 10%, 9%, 8%, 7%, 6%, 5% of the parameter representing the expression level. If the amount is within 4%, 3%, 2%, or 1%, then at least one of the inflammasome tannins. The expression level of the protein is the expression level of one or more control AD ​​biomarkers. The method according to claim 27, which is similar to the level.

29. The expression levels of the one or more control AD ​​biomarkers are obtained from the patient. The method according to claim 27, wherein the measurement is performed in the biological sample.

30. The expression levels of the one or more control AD ​​biomarkers mentioned above are those previously diagnosed with AD. The method according to claim 27, wherein the measurement is performed in a biological sample obtained from a severed individual.

31. The biological samples obtained from individuals previously diagnosed with AD are those that have contracted AD. The claim is for a biological sample of the same type obtained from the aforementioned patient suspected of having the condition. The method described in item 30.

32. The expression level of at least one inflammasome protein and one or more of the above. The expression levels of the control AD ​​biomarkers are obtained from organisms that were obtained from the control. The expression level of at least one inflammasome protein in the scientific sample and If the expression levels of one or more control AD ​​biomarkers are enhanced, please contact us. The method described in item 27.

33. The biological sample obtained from the control is suspected to be suffering from AD. The biological sample of the same type obtained from the aforementioned patient, as described in claim 32. method.

34. The aforementioned control is a healthy individual, and the healthy individual exhibits clinical symptoms consistent with AD. The method according to claim 32, wherein the individual is not one that has not performed the procedure.

35. The expression level of at least one inflammasome protein and one or more of the above. The expression level of the control AD ​​biomarker is the at least one infrastructure The masome protein and the one or more control AD ​​biomarkers specified The method according to claim 27, wherein the reference value or range of reference values ​​is augmented.

36. A parameter representing the expression level of at least one inflammasome protein. - and parameters representing the expression level of one or more control AD ​​biomarkers The method according to claim 32, wherein 'Tar' is the area under the curve (AUC).

37. The method according to claim 27, wherein the patient exhibits clinical symptoms consistent with AD.

38. The biological samples obtained from the patient suspected of having AD were from the brain and spinal cord. Liquid (CSF), CNS microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EV) The method according to claim 27, which is as follows.

39. The at least one inflammasome protein and / or the one or more controllers The expression level of the AD biomarker is determined by the expression level of at least one inflammasome Directed to proteins and / or one or more of the control AD ​​biomarkers The method according to claim 27, measured by an immunoassay using one or more antibodies. 。

40. The aforementioned at least one inflammasome protein is interleukin 18 (IL- 18) Apoptosis-related specular type containing IL-1β caspase recruitment domain The method according to claim 27, which is protein (ASC), caspase-1, or a combination thereof. Law.

41. The at least one inflammasome protein described in claim 27 includes an ASC. Method of loading.

42. Claim 27, wherein the at least one inflammasome protein comprises IL-18. Methods used.

43. The one or more control AD ​​biomarkers mentioned above are neurofilament light poly Peptides (NFL), soluble APP-alpha (sAPPα) and / or soluble APP- The method according to claim 27, wherein the molecule is beta (sAPPβ).

44. The at least one inflammasome protein is an ASC, and the one or more The control AD ​​biomarker shown above is soluble APP-alpha (sAPPα). The AUC of ASC is 0.833, and the AUC of sAPPα is 0.95 The method according to claim 36, wherein the answer is 6.

45. The at least one inflammasome protein is an ASC, and the one or more The control AD ​​biomarker above is soluble APPβ (sAPPβ), and ASC The AUC of is 0.833, and the AUC of sAPPβ is 0.

919. The method according to claim 36.

46. The at least one inflammasome protein is an ASC, and the one or more The control AD ​​biomarker above is neurofilament light polypeptide (N FL) is, the AUC of ASC is 0.833, and the AUC of NFL is, The method according to claim 36, wherein the coefficient is 0.

717.

47. The biological sample obtained from the patient is serum, and the patient is less Sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% The method according to claim 27, selected as having AD with a specificity of at least 55%.

48. The biological sample obtained from the patient is serum, and the patient is less A with sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% The method according to claim 27, which is selected as having D.

49. The biological sample obtained from the patient is serum, and the patient is less Both are selected as having AD with a sensitivity of 70% and a specificity of at least 55%, according to the claim. The method described in item 27.

50. The aforementioned specificity and / or sensitivity are determined using a receiver operating characteristic (ROC) curve with a 95% confidence interval. The method according to claim 47, which is determined by the method described.

51. In order to select the patient as having AD, the presence of one or more symptoms related to AD The method according to claim 27, further comprising evaluating the

52. One or more of the above symptoms related to AD include amnesia, lack of concentration, anxiety, anxiety when making decisions, or Confusion, difficulty understanding instructions or planning things, difficulty moving in unfamiliar environments, difficulty performing tasks, reading Forgetting immediate documents, loss or misplacement of valuables, difficulty organizing, confusion of time or place, bladder or This includes difficulty controlling bowel movements, personality or behavioral changes, such as mood or personality changes. Changes, changes in sleep patterns, communication difficulties, such as vocabulary problems in conversation or writing. Topics include: vulnerability to infection, impulsive or suspicious judgment, difficulty understanding visual images and spatial relationships, misplacement of objects, and Loss of ability to reverse a process, impaired or poor judgment, withdrawal from work or social activities. The method according to claim 51.

53. A parameter representing the expression level of at least one inflammasome protein. - and the parameter representing the expression level of the one or more control MCI biomarkers The method according to claim 32, wherein the meter is a cutoff value.

54. The at least one inflammasome protein is an ASC, and the cut The OFF value is greater than 264.9 pg / ml and less than 560 pg / ml, as described in claim 55. The method.

55. A parameter representing the expression level of at least one inflammasome protein. - and the parameter representing the expression level of the one or more control MCI biomarkers The method according to claim 32, wherein the meter is a cutoff value.

56. The at least one inflammasome protein is an ASC, and the cut The method according to claim 55, wherein the off-value is greater than 560 pg / ml.

57. Determine whether the patient has mild cognitive impairment (MCI) or Alzheimer's disease (AD). A method comprising at least one insect in a biological sample obtained from the patient Measuring the expression level of ramosome protein and the small amount in the biological sample The expression level of at least one inflammasome protein This involves comparing the phramosome protein to a predetermined reference value or a range of reference values, The expression level of the at least one inflammasome protein is the predetermined reference value If it is within the range, AD is used, or if the expression level exceeds a predetermined reference value, M is used. A method comprising selecting the patient as having CI.

58. The at least one inflammasome protein is an ASC, as described in claim 57. Method of loading.

58. The range of the predetermined reference value is 264.9 pg / ml to 560 pg / ml, claim. The method described in 58.

59. The method according to claim 58, wherein the predetermined reference value is greater than 560 pg / ml.

60. A method for evaluating a patient suspected of having age-related macular degeneration (AMD), wherein the patient is obtained Expression levels of at least one inflammasome protein in the biological samples To measure; and to determine the presence or absence of a protein signature associated with AMD. Therefore, the protein signature is the at least one inflammasome. The determination of the elevated levels of protein; and the determination of the patient that the protein If a signature is present, the patient is selected as having AMD. method.

61. The biological samples obtained from the aforementioned patients were cerebrospinal fluid (CSF) and CNS microdialysis. The extracellular vesicle (EV) derived from liquid, saliva, serum, plasma, urine, or serum, as described in claim 60. method.

62. The at least one inflammasome protein in the protein signature The aforementioned level is the at least one inflammasome in the protein signature. Measured by an immunoassay using one or more antibodies directed against a protein. The method according to claim 60.

63. The at least one inflammasome protein in the protein signature The aforementioned level is the level of at least one of the biological samples obtained from the control. The method according to claim 60, which is enhanced with respect to the level of phramosome protein.

64. The biological samples obtained from the aforementioned controls include cerebrospinal fluid (CSF) and CNS. Claim 63, which is microdialysis fluid, saliva, serum, plasma, urine, or serum-derived extracellular vesicles (EVs). Methods used.

65. The control is a healthy individual that does not exhibit clinical symptoms of AMD, according to claim 63. Method of description.

66. The aforementioned at least one inflammasome protein is interleukin 18 (IL- 18) Apoptosis-related specular type containing IL-1β caspase recruitment domain The method according to claim 60, which is protein (ASC), caspase-1, or a combination thereof. Law.

67. The above at least one inflammasome protein comprises ASC, and the AUC of ASC The method according to claim 60, wherein the coefficient is 0.9823.

68. The aforementioned at least one inflammasome protein includes IL-18, and IL-18 The method according to claim 60, wherein the AUC is 0.7286.

69. The biological sample obtained from the patient is serum, and the patient is less A with sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% The method according to claim 60, selected as having MD.

70. The biological sample obtained from the patient is serum, and the patient is less Sensitivity of 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% The method according to claim 60, selected as having AMD with a specificity of at least 55%. 。

71. The aforementioned specificity and / or sensitivity are determined using a receiver operating characteristic (ROC) curve with a 95% confidence interval. The method according to claim 69, which is determined by the method described.

72. To select the patient having AMD, the presence of one or more symptoms related to AMD is considered. The method according to claim 60, further comprising evaluation.

73. One or more of the above symptoms related to AMD include blurred vision, "indistinct vision, straight lines appearing wavy or distorted." And what you can see, blurred areas on the printed page, whether you can read the details at low light levels Or difficulty seeing, extra perception of bright, dark or blurred areas in the visual center. The method according to claim 72, wherein the whiteout or change in color perception is centered on the visual system.

74. A parameter representing the expression level of at least one inflammasome protein. The method according to claim 60, wherein - is a cutoff value.

75. The at least one inflammasome protein is an ASC, and the cut The method according to claim 74, wherein the OFF value is greater than 365.6 pg / mL.

76. The at least one inflammasome protein is IL-18, and the k The method according to claim 74, wherein the off-season value is greater than 242.4 pg / mL.

77. A method for treating inflammatory aging in a subject, wherein a therapeutically effective amount is specifically linked to ASC. This includes administering a monoclonal antibody or an antibody fragment thereof to the subject, The antibody or antibody fragment comprises a heavy chain variable (VH) region and a light chain variable (VL) region. Including the region, The VH region amino acid sequences are HCDR1 in SEQ ID NO: 6, HCDR2 in SEQ ID NO: 7, and the sequence Number 8 HCDR3 or HCDR1, HCDR2 and / or HCDR3 at least These variants include those having one amino acid substitution, The VL region amino acid sequences are LCDR1 of SEQ ID NO: 12, LCDR2 of SEQ ID NO: 13, and Sequence ID 14 LCDR3 or LCDR1, LCDR2 and / or LCDR3 These variants include those having at least one amino acid substitution, A method for treating inflammatory aging in the subject by administering the aforementioned drug.

78. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , Sequence IDs 18, 19, 20, 21, 22 or Sequence IDs 18, 19, 20, 21 or At least 95%, 96%, 97%, 98%, or 99% of the 22 amino acid sequences Containing the same amino acid sequence, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , SEQ ID NOs. 28, 29, 30, 31 or the amino acids of SEQ ID NOs. 28, 29, 30 or 31 At least 95%, 96%, 97%, 98%, or 99% of the amino acids in the acid sequence are identical. The method according to claim 77, comprising an acid sequence.

79. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 18 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is: At least 95%, 96%, and 97% of the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO:

28. The method according to claim 77, comprising %, 98%, or 99% identical amino acid sequences.

80. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 18 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 29 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

81. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 18 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 30 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

82. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 18 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 31 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

83. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 19 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

84. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 19 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence is relative to SEQ ID NO: 29 or the amino acid sequence of SEQ ID NO: 29 Containing at least 95%, 96%, 97%, 98%, or 99% identical amino acid sequences, The method according to claim 77.

85. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 19 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 30 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

86. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 19 or SEQ ID NO: 19 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 31 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

87. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 20 or SEQ ID NO: 20 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

88. The VH region amino acid sequence is relative to SEQ ID NO: 20 or the amino acid sequence of SEQ ID NO: 20 Containing at least 95%, 96%, 97%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence is relative to SEQ ID NO: 29 or the amino acid sequence of SEQ ID NO: 29 Containing at least 95%, 96%, 97%, 98%, or 99% identical amino acid sequences, The method according to claim 77.

89. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 20 or SEQ ID NO: 20 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 30 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

90. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 20 or SEQ ID NO: 20 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 31 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

91. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 21 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

92. The VH region amino acid sequence is relative to SEQ ID NO: 21 or the amino acid sequence of SEQ ID NO: 21 Containing at least 95%, 96%, 97%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence is relative to SEQ ID NO: 29 or the amino acid sequence of SEQ ID NO: 29 Containing at least 95%, 96%, 97%, 98%, or 99% identical amino acid sequences, The method according to claim 77.

93. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 21 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 30 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

94. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 21 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 31 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

95. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 22 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 28 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

96. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 22 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 29 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

97. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 22 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 30 or SEQ ID NO: 30 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

98. The VH region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 22 Containing 7%, 98%, or 99% identical amino acid sequences, The VL region amino acid sequence of the monoclonal antibody or the antibody fragment thereof is , at least 95%, 96%, 9% of the amino acid sequence of SEQ ID NO: 31 or SEQ ID NO: 31 The method according to claim 77, comprising 7%, 98%, or 99% identical amino acid sequences.

99. The method according to claim 77, wherein the ASC is a human ASC protein.

100. The antibody fragment is Fab, F(ab') ２ ,Fab',scFv, single domain The method according to claim 77, wherein the antibody is a nascent antibody, a diabody, or a single-chain camelid antibody.

101. The monoclonal antibody or the antibody fragment thereof is human, humanized, or chimeric. A method according to claim 77.

102. The administration of the monoclonal antibody or its antibody fragment is less than The method according to claim 77, which also reduces the level of inflammatory cytokines.

103. The administration of the monoclonal antibody or the antibody fragment thereof is performed in the target odor The method according to claim 77, which results in inhibition of inflammasome activation.

104. The administration of the monoclonal antibody or the antibody fragment thereof is controlled by a control and The method according to claim 77, which results in a reduction of ASC activity by comparison.

105. The method according to claim 104, wherein the control is an untreated subject.

106. The administration is by intraventricular, intraperitoneal, intravenous, or inhalation, as described in claim 77. method.

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