25 results about "Citrullination" patented technology

The invention discloses application of citrullinated endolectin-1 polypeptide in preparation of rheumatoid arthritis diagnosis products, and belongs to the technical field of rheumatoid arthritis diagnosis. The amino acid sequence of the citrullinated endolectin-1 polypeptide is GD-Cit-WSSQQGSKAVYPE, and the amino acid sequence of the citrullinated endolectin-1 polypeptide is GD- The product is used for detecting the content of the anti-citrullinated endolectin-1 polypeptide antibody in a biological sample of a patient, and the antibody level is remarkably different from that of normal healthy people and other common rheumatism immune disease patients easily confused with rheumatoid arthritis in the body of an RA patient. The kit has good sensitivity for common RA, RA with normal ESR and CRP, and anti-CCP antibody / RF negative RA patients, and has good supplementary diagnostic value for RA diagnosis.

The invention discloses application of SMCP in preparation of a rheumatoid arthritis diagnosis product, an anti-SMCP antibody in a biological sample of a patient is used as a marker, and the diagnosis product is used for detecting the content of the anti-SMCP antibody. The SMCP is a polypeptide mixture which is prepared from citrullinated SR-A polypeptide, citrullinated MCV polypeptide, citrullinated caspase14 polypeptide and citrullinated PCOLCE polypeptide. According to the present invention, the anti-SMCP antibody can be subjected to one-time detection so as to achieve the accurate diagnosis of rheumatoid arthritis (RA); besides, the anti-SMCP antibody also has better auxiliary diagnostic value for RA patients with negative anti-CCP antibody, and when the anti-SMCP antibody and the anti-CCP antibody are combined for diagnosis, the RA detection rate can be further improved under the condition of keeping high specificity, and the targets of early diagnosis, early treatment and reduction of disability rate can be more favorably realized.

Disclosed herein are high performance biomarkers and kits for the early detection of small cell lung cancer (SCLC), which can be used to identify, diagnose and treat SCLC patients in the early stage. Methods of diagnosing and treating SCLC in a subject can include detecting the presence of an autoantibody that specifically binds to one or more epitopes of an antigen in a biological sample obtained from the subject, wherein the one or more epitopes of the antigen comprise a post-translational modification; diagnosing the subject with SCLC when the presence of the autoantibody is detected in the biological sample; and treating the SCLC in the subject by administering a chemotherapy regimen, an immunotherapy regimen, an antibody, surgical and / or radiation therapy. In one example, post-translational modifications targeted by autoantibodies include citrullination, isoaspartic acidification, and / or cancer-specific glycosylation.

The invention provides antibodies or binding fragments thereof directed against citrulline-containing epitopes. The antibodies or binding fragments thereof of the invention can be used in therapy, for example in the treatment or prevention of Neutrophil Extracellular Trap (NET)-associated pathologies.

The invention discloses a novel nuclear magnetic resonance contrast agent Gd-DOTA-PP for targeting citrullinated histone to achieve neutrophil extracellular trap net imaging and a preparation method and application thereof.The method comprises the steps that citrullinated histone targeting polypeptide PP and ligand molecules DOTA-NHS are combined, and a compound DOTA-PP is obtained; and then gadolinium (Gd) ions are introduced into the DOTA-PP through a coordination reaction, and the novel contrast agent Gd-DOTA-PP is prepared. The contrast agent can be selectively combined with an important marker, namely citrullinated histone, of neutrophil extracellular trapping nets (NETs), and T1 weighted imaging signals of a target area are remarkably enhanced. The preparation method is simple and convenient to operate, the preparation process is highly controllable, and the obtained contrast agent has excellent biocompatibility and targeting characteristic. The accurate targeting ability of the probe enables the influence signal of the probe in NETs enrichment areas such as tumor early metastasis, tumor infiltration lymph nodes and the like to be obviously enhanced, a powerful tool is provided for tumor diagnosis, especially accurate diagnosis of the early metastasis, and the probe has important clinical application value.

The present invention discloses citrullinated SAA polypeptides and their application in the preparation of diagnostic products for rheumatoid arthritis. The amino acid sequence of the citrullinated SAA polypeptide is: DKYFHA-Cit-GNYDAAK-Cit-GPGGA. Through this polypeptide, the present invention has identified the citrullinated autoantigen B cell epitope of SAA and the corresponding autoantibody, namely anti-citrullinated SAA polypeptide antibody (anti-CAP). The expression level of anti-CAP in RA patients is significantly higher than that in other disease control groups and healthy groups, and it has a good positive rate in early RA, ESR / CRP normal RA, and anti-CCP antibody / RF negative RA, providing a new strategy for the diagnosis of RA.

The application discloses citrullinated collagen type II polypeptide and application thereof. The amino acid sequence of the polypeptide is Ste-QYMCitADQAAGGLR (SEQ ID NO. 1), wherein the N terminal of glutamine Q in the sequence is connected with octadecanoic acid Ste, and the fourth position in the sequence is modified by citrullination. The citrullinated collagen type II polypeptide has a long drug half-life, can effectively treat rheumatoid arthritis, and has small side effects.

The application discloses application of citrullinated galectin-1 polypeptide in preparation of a rheumatoid arthritis diagnosis product, and belongs to the technical field of rheumatoid arthritis diagnosis. The amino acid sequence of the citrullinated galectin-1 polypeptide is GD-Cit-WSSQQGSKAVYPE; the product is used for detecting the content of anti-citrullinated galectin-1 polypeptide antibody in a biological sample of a patient, and the antibody level is significantly different between RA patients, normal healthy people and other common rheumatic immune disease patients who are easily confused with rheumatoid arthritis. The product has good sensitivity to common RA, RA with normal ESR and CRP, and anti-CCP antibody / RF negative RA patients, and has good supplementary diagnosis value for the diagnosis of RA.

To provide antibodies or binding fragments thereof directed against citrulline-containing epitopes.SOLUTION: An antibody or binding fragment thereof that specifically binds to a citrullinated epitope on deiminated human histone 2A and / or histone 4 comprises CDR having a particular amino acid sequence. The antibodies or binding fragments thereof of the present invention can be used in therapy, for example, in the treatment or prevention of Neutrophil Extracellular Trap (NET)-associated pathologies.SELECTED DRAWING: None

The present invention relates to C-X-C motif chemokine ligand 10 (CXCL10) binding proteins and their use in methods of detecting and / or diagnosing a condition in a subject, including determining the level of CXCL10 in a subject. Specific antibodies that bind total CXCL10 (full length, N-terminally truncated and citrullinated) and antibodies that bind active CXCL10 (full length) are used to measure the level of total CXCL10 and active CXCL10 in ovarian cancer patient samples. The calculated ratio between active CXCL10 and total CXCL10 is lower in patients with malignant disease compared to patients with benign tumors or healthy individuals, and this calculated ratio is the basis for methods of diagnosing malignant disease, monitoring tumor burden and disease progression.

The present invention relates to a CXCR4 inhibitor compound for use in the treatment of a severe acute respiratory distress syndrome (sARDS), wherein the sARDS is characterized by a dysregulation of NETosis which may be measured by the plasmatic levels of cDNA, citrullinated histone H3, neutrophil elastase, interleukin-8, myeloperoxidase-DNA complexes and / or calprotectin. The present invention also relates to a method of prognostic of severe ARDS, a pharmaceutical composition for use in the treatment of severe acute respiratory distress syndrome (ARDS), a kit of prognostic of severe ARDS in a subject and the use of NETosis biomarkers.

The present invention relates to a CXCR4 inhibitor compound for use in the treatment of a severe acute respiratory distress syndrome (sARDS), wherein the sARDS is characterized by a dysregulation of NETosis which may be measured by the plasmatic levels of cDNA, citrullinated histone H3, neutrophil elastase, interleukin-8, myeloperoxidase-DNA complexes and / or calprotectin. The present invention also relates to a method of prognostic of severe ARDS, a pharmaceutical composition for use in the treatment of severe acute respiratory distress syndrome (ARDS), a kit of prognostic of severe ARDS in a subject and the use of NETosis biomarkers.

Disclosed herein are chimeric antigen receptors (CARs) comprising an antigen binding site that recognizes citrullinated polypeptides. Citrullinated polypeptides, such as citrullinated vimentin, are expressed in the skin lesions of subjects with hidradenitis suppurativa. Further disclosed are T cells, and in particular, Treg cells that express these CARs. Administration of these CAR-T cells is useful in the treatment of hidradenitis suppurativa.

The present disclosure relates to anti-CitH3 (citrullinated histone H3) antibodies, antigen binding fragments and uses thereof.

Disclosed herein are high-performance biomarkers and panels for the early detection of small cell lung cancer (SCLC), which are useful for identifying, diagnosing, and treating SCLC patients at an early stage. A method for diagnosing and treating SCLC in a subject includes detecting the presence of an autoantibody that specifically binds to one or more epitopes of an antigen in a biological sample obtained from the subject, where the one or more epitopes of the antigen comprise a post-translational modification; diagnosing the subject as having SCLC if the presence of the autoantibody is detected in the biological sample; and treating the SCLC in the subject by administering a chemotherapy regimen, an immunotherapy regimen, an antibody, performing surgery, and / or performing radiation therapy. In one example, the post-translational modifications targeted by the autoantibody include citrullination, isoaspartylation, and / or cancer-specific glycosylation.

The application discloses citrullinated T200C polypeptide and application thereof in preparation of a rheumatoid arthritis diagnosis product, and belongs to the technical field of disease diagnosis. The amino acid sequence of the citrullinated T200C polypeptide is as follows: GSM-Cit-GA-Cit-Cit-EPEEPEGAV. Research finds that the level of anti-citrullinated T200C polypeptide antibodies in the body of RA patients is obviously higher than that of healthy people and other rheumatic immune disease patients who are easily confused with RA. Taking the citrullinated T200C polypeptide of the application as a detection antigen, detection of anti-citrullinated T200C polypeptide antibodies in the body of patients can effectively identify RA, especially for RA with negative anti-CCP antibodies and / or RF, and normal ESR and / or CRP RA, and has good diagnostic value.

The invention relates to a hybrid molecule comprising at least one antibody Fc fragment covalently linked to at least one fibrin-derived peptide comprising at least one citrullyl residue, the uses of such a hybrid molecule, and its production process.

Embodiments provide for devices and methods of use for detecting one or more biomarkers of rheumatic disease in a subject and managing rheumatic disease in a subject. In an example, a method or a portion thereof includes detecting citrullinated human serum albumin (HSA) in a biological sample via obtaining the biological sample from a subject, applying the biological sample to a lateral flow device under conditions sufficient for formation of an immunocomplex comprising anti-HSA antibody coupled to citrullinated HSA that is in turn coupled to anti-citrullinated HSA autoantibody, determining a quantity of the immunocomplex, and managing rheumatic disease associated with the subject. In this way, rheumatic disease may be effectively managed based at least in part on amounts of citrullinated HSA detected via rapid point-of-care test methodology.

The invention discloses a lignin carbon fiber-based microneedle electrode which comprises a working microneedle electrode, a counter microneedle electrode and a reference microneedle electrode, the working microneedle electrode is a specific biological recognition interface constructed by depositing gold on a microneedle substrate, bridging through a sulfydryl-polyethylene glycol-carboxyl self-assembled molecular layer and covalently coupling an H3Cit antibody by utilizing an NHS / EDC.HCl activation method; the microneedle substrate is prepared by ball-milling lignin carbon fibers, ultrasonically dispersing the lignin carbon fibers in a dichloromethane solution of a polylactic acid-glycolic acid copolymer to obtain slurry, injecting the slurry into a microneedle array mold, and performing vacuum defoaming. The invention discloses a three-electrode sensor which comprises a working electrode, a reference electrode and a counter electrode, and a working microneedle electrode is used as the working electrode. The invention discloses an application of a three-electrode sensor in detection of H3Cit. The lignin carbon fiber-based microneedle electrode disclosed by the invention is regular in arrangement, good in mechanical property and capable of effectively identifying H3Cit.

Provided are anti-PAD4 antibodies having excellent properties and an excellent method for treatment of RA. Used are anti-PAD4 antibodies that specifically bind to an epitope containing positions 345, 347, and 348 of PAD4. These anti-PAD4 antibodies may inhibit the citrullination activity of PAD4. In addition, these anti-PAD4 antibodies may have a KD (M) of 9.0×10−9 or less. Optionally, the anti-PAD4 antibody and a TNFα inhibitor are used in combination.

Described herein are methods and kits for diagnosing or determining a progression of rheumatoid arthritis (RA), comprising detecting or determining levels of autoantibodies specific to citrullinated-CLEC12A (C- type lectin domain family 12 member A).

The present invention relates to a method for providing information for the diagnosis and / or prognosis of aortic valve stenosis, and was arrived at by discovering that an increase in anti-citrullinated peptide antibody levels is associated with the onset and prognosis of aortic valve stenosis. The present inventors discovered that the accurate early diagnosis of aortic valve stenosis is possible through measuring anti-citrullinated peptide antibody levels, and the degree of aortic valve deformity, severity, and probability of complications such as hypertension, rheumatoid arthritis, and interstitial lung disease can be predicted, and thus the anti-citrullinated peptide antibody is expected to be used as a biomarker for more effective diagnosis, prognosis, and treatment of aortic valve stenosis.

The disclosure relates to novel citrullinated polypeptides that bind to anti-citrullinated protein antibodies (ACPAs) and their use in the diagnosis and prediction of rheumatoid arthritis.