219 results about "Systemic lupus erythematosus" patented technology

The invention discloses a method for constructing a Ddx58-R109C point mutation mouse model by using a CRISPR / Cas9 gene editing technology and an application of the Ddx58-R109C point mutation mouse model. The method comprises the following steps: (1) target construction: searching a CDS region of a Ddx58 gene, determining an exon part, and determining a gene mutation site; (2) obtaining a fertilized egg, and injecting Cas9mRNA, gRNA and donor oligo into the fertilized egg of the C57BL / 6J mouse together in vitro through a microinjection technology to obtain an F0-generation hybrid mouse; (3) mating the F0-generation hybrid mouse with the wild type mouse to obtain an F1-generation mouse; (4) the F1-generation heterozygous mice which are identified to be positive are subjected to mating, and homozygous Ddx58-R109C mutant type and wild type mice can be obtained by breeding obtained offspring; (5) phenotypic analysis shows that Ddx58-R109C point mutation mice can have pathological changes of systemic lupus erythematosus and lupus nephritis; the invention can provide an effective research approach and method for researchers to deeply explore the action mechanism of Ddx58-R109C mutation in diseases, and has important significance for explaining the pathogenesis of systemic lupus erythematosus and researching and developing targeted therapeutic drugs.

The invention discloses a method for constructing a differential diagnosis model for lupus nephritis and membranous nephropathy, and belongs to the technical field of intelligent medical treatment. The modeling method comprises the following steps: S1, respectively collecting flow cytometry detection data of lupus nephritis patients and healthy control personnel; s2, performing data cleaning and conversion on the flow cytometry detection data, and converting non-numerical features into digits; carrying out implication on the missing value by adopting a k nearest neighbor algorithm from an implication packet; s3, random sampling is carried out on the cleaned and converted data set, and samples are divided into a training set and a verification set according to the proportion of 7: 3; s4, dividing a training subset and a test set from the training set, and iteratively selecting the types of cells incorporated into the constructed model as pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T, and CD38 + PD-1 + CD8T by adopting an RFE method, wherein the types of the cells incorporated into the constructed model are pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T and CD38 + PD-1 + CD8T; and S5, performing a classification task by adopting TabPFNClassifier, performing training from features selected from the training data set, then evaluating the performance of the model, performing model training by utilizing detection data, and performing evaluation to construct a lupus nephritis prediction model with high accuracy.

Provided is a method for estimating a factor causing an abnormality in coagulation of a blood sample. In the method, 1) a parameter Ps relating to a coagulation reaction in a sample S and a parameter Pm relating to a coagulation reaction in a sample M are calculated, 2) an estimation as to whether the sample S is coagulation-factor-inhibitor-positive is carried out on the basis of Ps, and 3) a sample S that is not estimated to be coagulation-factor-inhibitor-positive in 2) is estimated to be lupus-anticoagulant-positive or coagulation-factor-deficient on the basis of Pm or on the basis of Ps and Pm. The sample S is a test blood sample having an extended coagulation time, the sample M is a mixed sample of the sample S and a sample N, and the sample N is a normal blood sample. Ps is calculated on the basis of a measurement point or time at which a coagulation reaction curve or a coagulation speed curve of the sample S reaches a prescribed value, and Pm is calculated on the basis of a measurement point or time at which a coagulation reaction curve or a coagulation speed curve of the sample M reaches a prescribed value.

The present disclosure provides a method for assessing a lupus state of a patient, the method comprising: analyzing a data set comprising and / or derived from gene expression measurements of at least 2 genes selected from genes listed in Tables: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30; 31; and 32, to classify the lupus state of the patient, wherein the gene expression measurements are obtained from a biological sample obtained or derived from the patient.

The present invention relates to double stranded oligonucleotides that are complementary to JAK1, leading to modulation of the expression of JAK1. Modulation of JAK1 expression is beneficial for a range of medical disorders including inflammatory bowel disease, organ transplant rejection, graft-versus-host disease, multiple sclerosis, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriasis, dermatitis, diabetic nephropathy, systemic lupus erythematosus (SLE), dry eye disease, cancer, myelofibrosis, and asthma. Also included are compositions comprising the double stranded oligonucleotide and methods of treatment using the double stranded oligonucleotide.

The invention relates to the technical field of detection kits, in particular to a blood coagulation reaction linked lupus anticoagulant fluorescence detection kit and application thereof, the kit contains a screening-confirmation integrated reagent, a calibration product, a quality control product and an anticoagulation interference inhibitor; the integrated reagent is divided into a reagent A and a reagent B, the reagent A contains a buffer solution, recombinant snake venom thrombin, composite phospholipid, a fluorescent substrate and other components, and the reagent B contains prothrombin, calcium ions, high-concentration composite phospholipid and other components; the composite phospholipid system is formed according to a specific proportion and modifies beta2-glycoprotein I, the fluorescence enhancement-stabilization system is formed by matching a Schiff base compound with a stabilizer, the calibrator is a series of lupus anticoagulant standard substances, and the quality control substance comprises simulants with different concentrations and negative control. The anti-interference capability is high, and the influence of anti-coagulant drugs and enzyme source fluctuation is reduced; the signal amplification effect is obvious, the detection sensitivity is high and the reagent stability is good; the operation is simple and convenient, screening and confirmation are integrally completed, and a conventional fluorescence detector is adapted.

The invention relates to a lupus anticoagulant detection system and method based on a conventional blood coagulation reagent, and relates to the technical field of detection.The lupus anticoagulant detection method comprises the steps that a user sample is collected, the conventional blood coagulation reagent is adopted for conducting anticoagulant detection on the user sample, and a detection standardization ratio is obtained; acquiring similar detection data in historical time, and performing fuzzy error analysis on the detection standardization ratio by adopting a historical detection standardization ratio set in the historical detection data to obtain a fuzzy error coefficient; calculating to obtain a reagent error correction coefficient according to the fuzzy error coefficient and the conventional blood coagulation reagent error; and according to the fuzzy error coefficient, acquiring anticoagulation treatment characteristic information of the user, analyzing to obtain a user error correction coefficient, combining with a reagent error correction coefficient, performing error correction calculation on the detection standardization ratio, and obtaining a correction detection standardization ratio interval as a detection result. The technical problems that lupus anticoagulant detection conditions are deficient and the detection efficiency is low in the prior art are solved.

The invention provides systems and methods for diagnosing and treating an inflammatory skin disease in a patient. The described methods may be used for longitudinal monitoring of the development, progression, or regression of a skin disease including lupus, psoriasis, atopic dermatitis, and systemic sclerosis (scleroderma) condition in a patient, in response to a therapy administered for the condition.

A method for characterizing disease activity in a systemic lupus erythematosus patient (SLE), comprising obtaining a dataset associated with a blood, serum, plasma or urine sample from the patient, assessing the dataset for a presence or an amount of protein expression of at least one innate serum or plasma mediator, assessing the dataset for a presence or an amount of protein expression of at least one adaptive serum or plasma mediator biomarker, assessing the dataset for a presence or an amount of at least one chemokine / adhesion molecule biomarker, assessing the dataset for a presence or an amount of at least one soluble TNF superfamily biomarker, assessing the dataset for a presence or an amount of at least one inflammatory mediator biomarker, assessing the dataset for a presence or an amount at least one SLE-associated autoantibody specificity biomarker and calculating a Lupus Disease Activity Immune Index (LDAII) score.

The present disclosure provides methods for treating lupus nephritis in an individual that has lupus. In some embodiments, the methods comprise administering to the individual an effective amount of a type II anti-CD20 antibody. In other aspects, the present disclosure provides methods for treating membranous nephropathy.

The invention discloses a biomarker for diagnosing systemic lupus erythematosus and lupus nephritis and application of the biomarker, and relates to the technical field of biological medicines. The biomarker is an ISG15hiCD16 < + > mononuclear cell. According to the application disclosed by the invention, the ISG15hiCD16 + mononuclear cell subpopulation is found to be obviously increased in an SLE (systemic lupus erythematosus) patient. The invention also finds that the expression level of the ISG15hiCD16 + mononuclear cell subpopulation is positively correlated with the disease activity of the SLE patient, and the expression level of the ISG15hiCD16 + mononuclear cell subpopulation of the SLE patient with the kidney enduring expression is obviously higher than that of the SLE patient without the kidney enduring expression. The working characteristic curve analysis of a subject shows that the ISG15hiCD16 + mononuclear cell subset has better sensitivity and specificity for diagnosing the SLE and the LN, and has important significance for clinical auxiliary diagnosis of the SLE and the LN and illness state evaluation.

The invention relates to the technical field of biological diagnosis, and discloses application of a marker and a magnetic particle chemiluminescence kit for diagnosing neuropsychiatric lupus, and the marker is adenosine homocysteine enzyme 2; the kit comprises a calibration product, a quality control product, an enzyme-labeled secondary antibody, a magnetic particle reagent and a chemiluminescent substrate, the enzyme-labeled secondary antibody is an adenosine homocysteine enzyme 2 antibody labeled by alkaline phosphatase and is used for detecting a marker; the magnetic particle reagent is an adenosine homocysteine enzyme 2 antibody coated by magnetic particles and is used for separating a marker; the adenosine homocysteine enzyme 2 disclosed by the invention can be used as a marker for diagnosing systemic lupus erythematosus complication neuropsychiatric lupus. A kit obtained by adopting the marker can effectively distinguish NPSLE from other types of neuropsychiatric diseases by detecting the expression level of SAHH2, and help is provided for early diagnosis, disease monitoring and treatment evaluation.

The invention provides an application of a reagent for detecting an effector CD4 + T cell in peripheral blood of a subject in preparation of a product for diagnosing membranous nephropathy, lupus nephritis or ANCA-related vasculitis. The invention also provides an application of the effector CD4 + T cell in peripheral blood in preparation of a diagnostic model for diagnosing membranous nephropathy, lupus nephritis or ANCA-related vasculitis. The marker is detected through flow cytometry, and the result shows that the Ejector CD4 + T cell is remarkably increased in a patient with membranous nephropathy, can effectively distinguish membranous nephropathy from healthy control (verification set AUC 0.8098), can assist in identifying membranous nephropathy, lupus nephritis (verification set AUC 0.8686) and ANCA-related vasculitis (verification set AUC 0.8968), and the level of the Ejector CD4 + T cell is related to whether membranous nephropathy is difficult to treat or not.

The present disclosure provides systems and methods for classifying lupus disease state of a patient is disclosed. The method can include analyzing a patient data set comprising or derived from gene expression measurements data of at least 2 genes, from a biological sample obtained or derived from the patient, to classify the lupus disease state of the patient. The at least 2 genes can be selected from Tables 17-1 to 17-30, and / or Tables 24-1 to 24-30.

The invention discloses a lupus nephritis marker and application thereof, and belongs to the technical field of biomarkers. The marker for the lupus nephritis, disclosed by the invention, comprises one or more of CD8, CD38 and PD-1. By detecting specific cell surface markers in patient blood, early diagnosis of LN is assisted in a minimally invasive mode, and based on deep comparative analysis of LN patients and healthy people, the specificity and sensitivity of the biomarkers in LN diagnosis are ensured through screening of the biomarkers. In the aspect of differential diagnosis, a clinician is assisted to distinguish LN from other types of kidney diseases, such as membranous nephropathy (MN) and anti-neutrophil cytoplasm antibody related vasculitis (AAV), by analyzing specific biomarker modes of different nephropathy. The dependence on kidney puncture is reduced, related potential risks and inconvenience are avoided, and meanwhile more accurate and timely diagnosis is provided for an SLE patient.

The application provides a preparation of a sema7A monoclonal antibody 8A12 and a treatment effect of the sema7A monoclonal antibody 8A12 on lupus nephritis, wherein the CDR-H1 of the heavy chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 1, the CDR-H2 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 2, and the CDR-H3 of the heavy chain variable region is an amino acid sequence shown in SEQ ID No. 3; the CDR-L1 of the light chain variable region of the monoclonal antibody 8A12 is an amino acid sequence shown in SEQ ID No. 4, the CDR-L2 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 5, and the CDR-L3 of the light chain variable region is an amino acid sequence shown in SEQ ID No. 6. The monoclonal antibody 8A12 can effectively inhibit the expression up-regulation of IL-1beta, TNF-alpha and IL-6 caused by Sema7A recombinant protein, can effectively inhibit the macrophage inflammatory response induced by Sema7A, and can continuously and effectively reduce serum anti-double-stranded DNA antibodies and kidney damage of lupus mice. The monoclonal antibody 8A12 can be used for preparing a pharmaceutical composition for preventing and / or treating systemic lupus erythematosus and / or lupus nephritis thereof.

The present invention relates to compounds of formula (I), and stereoisomers, tautomers, N- oxides, and pharmaceutically acceptable salts thereof that are useful for modulating, preferably inhibiting three-prime repair exonuclease (TREX1). The present invention further relates to compounds of formula (I) for use as a medicament and to pharmaceutical compositions comprising said compounds. Further, the present invention relates to compounds of formula (I) and pharmaceutical compositions comprising said compounds for use in the treatment of cancer, such as breast, small cell lung cancer and colorectal cancer, in particular cancers with chromosomal instability, TREX1-mediated autoimmune diseases, inflammatory myocarditis, Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus (SLE) and retinal vasculopathy with cerebral leukodystrophy (RVCL).

The invention belongs to the technical field of biological medicines, and particularly relates to application and a method of PHF20 in preparation of a medicine for treating systemic lupus erythematosus and the medicine. The invention discloses an application of PHF20 in treatment of systemic lupus erythematosus, a lentivirus with murine PHF20 is selected as a gene therapy tool, an R848 induced lupus mouse model is taken as an experimental subject for gene therapy, and results show that injection of the overexpressed PHF20 lentivirus in a lupus mouse body has the following effects: (1) spleen swelling is improved, and spleen index is significantly reduced; (2) reducing urine protein, urea nitrogen level, anti-dsDNA antibody level and IgG antibody level of the model mouse; and (3) the pathological damage to the kidney of the model mouse is relieved. The research results show that the PHF20 serving as the target provides important reference value for potential application prospects in systemic lupus erythematosus gene therapy and even autoimmune disease gene therapy.

The present invention relates to compounds of formula 1: # imgabs0 # and their use as STING antagonists, for example, the composition is used for treating diseases selected from the group consisting of systemic lupus erythematosus (SLE), (single and double gene) interferon diseases (including STING-related vascular disease (SAVI), Aicardi-Goutires syndrome (AGS), COPA syndrome and familial chilblain-like lupus, DNASE2 or ATAD3A gene mutated type I interferon disease, age-related macular degeneration (AMD), retinopathy, glaucoma, lupus erythematosus, lupus erythematosus, lupus erythematosus, lupus erythematosus, lupus erythematosus, lupus erythematosus, lupus erythematosus, lupus erythematosus, lupus erythematosus, lupus erythematosus, and lupus erythematosus. Amyotrophic lateral sclerosis (ALS), diabetes, obesity, inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), Bloom syndrome, sicca syndrome, Parkinson's disease, heart failure and cancer, systemic sclerosis (SSc), dermatomyositis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic plus acute liver failure (ACLF), interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), and the like. , aging / muscle disease, sepsis, heart failure, rheumatoid arthritis, and osteoarthritis.

Disclosed herein is a method for treating, preventing, and / or slowing the progression of various chronic inflammatory condition groups including: (1) the Type 2 Diabetes group (Metabolic Syndrome (MET), obesity, hyperglycemia); (2) ARDS (Acute Respiratory Distress Syndrome); (3) chronic autoimmune inflammatory conditions (Rheumatoid Arthritis (RA), Lupus, and Psoriasis); (4) inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis; (5) metabolite group-mediated diseases (atherosclerosis, hypertension, and congestive heart failure); and (6) eating disorders, such as Prader-Willi Syndrome and other monogenic and symptomatic obesity disorders including leptin pathway defects, each method comprising orally administering a pharmaceutical composition comprising a denatonium salt. The present disclosure is based on the results of a series of studies that tracked biomarker cluster levels to track mediators of inflammatory conditions and mediators of gut signaling hormones in response to orally administered denatonium salts.

Methods are disclosed herein for modulating osteoclast fusion. In some embodiments, these methods include administering an effective amount of a Lupus autoantigen (La) protein, or an agent that modulates La protein expression or activity, to a subject in need thereof, thereby modulating osteoclast fusion in the subject. In some embodiments, the method increases osteoclast fusion and bone resorption. In other embodiments, the method decreases osteoclast fusion and bone resorption.

The invention relates to oil seal liquid and application thereof in blood coagulation detection, and belongs to the technical field of blood coagulation detection. The oil seal liquid can form a uniform film when covering a plasma sample, the activity of thrombin is not affected while air is isolated, and in addition, the oil seal liquid is a biological inert formula, is easy to clean and does not generate adsorption or reaction with blood coagulation factors and reagents. Therefore, the oil seal liquid and the sample are incubated synchronously in the pre-warming stage, and errors caused by sample evaporation and temperature fluctuation in the pre-warming stage can be reduced. Compared with traditional paraffin oil, the oil seal liquid can effectively isolate air to avoid sample evaporation and reduce reagent interference, is easy to clean, provides reliable technical support for blood coagulation factor deficiency and precise identification of inhibitors, and is suitable for APTT correction experiments, PT correction experiments or clinical detection and application of lupus anticoagulant (LA).

A composition for treating system lupus erythematosus (SLE) includes a plant virus-based nanoparticle engineered to express at least a tolerogenic peptide associated with SLE and a buffer, of which a method of manufacturing includes infecting a plant with a virus to produce the plant virus-based nanoparticle, sampling symptomatic leaves from the plant, homogenizing the plant virus-based nanoparticle, incubating the plant virus-based nanoparticle, centrifuging the plant virus-based nanoparticle, and filtrating the plant virus-based nanoparticle.

A method for identifying MRL / lpr lupus kidney organoid specifically comprises the following steps: collecting an organoid culture medium to be detected, detecting the levels of ANA and anti-ds-DNA antibodies in the culture medium, and carrying out histomorphological identification on the organoid. According to the invention, the histomorphology of the MRL / lpr lupus kidney organ of a mouse is identified by detecting the levels of ANA and an anti-ds-DNA antibody as well as HE staining and immunofluorescence, so that whether the MRL / lpr lupus kidney organ is successfully constructed or not is detected.

The application discloses a kind of biomarkers for evaluating systemic lupus erythematosus to lupus nephritis progression, prediction model and application, belong to lupus nephritis prediction technical field.The application provides a kind of for evaluating systemic lupus erythematosus to lupus nephritis progression prediction model, the prediction model is according to the ratio of biomarker CD8 / CD4 and the κ / λ ratio of naive B cell, carries out binary Logistic regression analysis, obtains LogitP value, by comparing the high and low of the LogitP value and critical value 0.66938, predicts systemic lupus erythematosus to lupus nephritis progression situation.The prediction model constructed in the application aims to identify the individuals in lupus patients who may develop into lupus nephritis.This innovative model not only provides important guidance in the diagnosis, prognosis prediction and efficacy evaluation of the disease, but also provides a new perspective for the clinical management of lupus nephritis.

The invention discloses a diagnostic marker for ANCA (Angiovasculitis) related vasculitis. It is found for the first time that the CD19 + CD38 + CD27-CD24 + cell can be used as the diagnosis marker of ANCA related vasculitis, and the diagnosis efficiency is high; in addition, it is found that the CD19 + CD38 + CD27-CD24 + cells can remarkably distinguish ANCA related vasculitis and membranous nephropathy or ANCA related vasculitis and lupus nephritis, a new direction is provided for diagnosis and subsequent treatment of ANCA related vasculitis, and the application has wide application prospects clinically.

The present disclosure provides systems and methods for classifying lupus disease state of a patient is disclosed. The method can include analyzing a patient data set comprising or derived from gene expression measurements data of at least 2 genes, from a biological sample obtained or derived from the patient, to classify the lupus disease state of the patient. The at least 2 genes can be selected from Tables 17-1 to 17-30, and / or Tables 24-1 to 24-30.

The present invention relates to novel heterocyclic compounds useful in the preparation of medicaments for the treatment of diseases associated with various functions of the histamine 4 receptor.In particular, said drugs are useful for treating inflammatory diseases, allergy, pain, nasal polyps, rhinitis, chronic sinusitis, nasal congestion, nasal itching, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis, eczema, pruritus, itchy skin, urticaria, idiopathic chronic urticaria, scleroderma, conjunctivitis, keratoconjunctivitis, ocular inflammation, dry eye, cardiac dysfunction, arrhythmia, atherosclerosis, multiple sclerosis, inflammatory bowel disease (including colitis, Crohn's disease, ulcerative colitis), inflammatory pain, neuropathic pain, osteoarthritis pain, autoimmune disease, thyroid, immune-mediated (also known as type I) diabetes, lupus, post-surgical adhesions, vestibular disorders and cancer.

The present invention relates to a composition for preventing or treating lupus or glomerulonephritis comprising a recombinant stabilized Galectin-9 protein. Specifically, the recombinant stabilized Galectin-9 protein of the present invention has been confirmed to exhibit safety in a systemic lupus erythematosus (SLE) animal model, reduce skin lesions, lymphadenopathy, and proteinuria caused by lupus, ameliorate lupus nephritis and glomerulonephritis, and decrease the concentration of anti-dsDNA antibodies in plasma. Accordingly, the recombinant stabilized Galectin-9 protein of the present invention can be effectively used as an active ingredient in a composition for preventing or treating lupus or glomerulonephritis.

The invention provides methods for treating or delaying progression of lupus nephritis in an individual that has lupus. In some embodiments, the methods comprise administering to the individual an effective amount of a type II anti-CD20 antibody. The invention also provides methods for treating or delaying progression of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in an individual. In some embodiments, the methods comprise administering an effective amount of an anti-CD20 antibody.