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IDENTIFICATION AND MEDICAL APPLICATIONS OF ANTI-CITRULLINATED-PROTEIN ANTIBODIES IN RHEUMATOID ARTHRITIS

机译:类风湿关节炎抗环丙氨酸抗体的鉴定和医学应用

摘要

Compositions and methods for detection of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients. Patient samples known or suspected of containing ACPAs were probed against citrullinated proteins, and antibody responses to 190 citrullinated proteins in 20 RA patients were investigated. Unique antibody reactivity patterns in both clinical anti-cyclic citrullinated peptide assay positive (CCP+) and negative (CCP-) RA patients were observed. At individual antigen levels, six novel antibody/antigen complexes were discovered and validated against specific citrullinated antigens (Myelin Basic Protein (MBP), osteopontin (SPP1), flap endonuclease (FENl), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGFl) and stanniocalcin-2 (STC2)) in RA patients. Identification of immune-dominant epitope(s) for citrullinated MBP was also performed. The identified biomarkers have high specificity, especially MBP.
机译:用于检测类风湿关节炎(RA)患者抗瓜氨酸化蛋白抗体(ACPA)的组合物和方法。对已知或怀疑含有ACPA的患者样本进行了瓜氨酸化蛋白的探测,并调查了20名RA患者对190种瓜氨酸化蛋白的抗体反应。在临床抗环瓜氨酸肽测定阳性(CCP +)和阴性(CCP-)RA患者中均观察到独特的抗体反应模式。在各个抗原水平上,发现并针对特定瓜氨酸化抗原(髓磷脂碱性蛋白(MBP),骨桥蛋白(SPP1),皮瓣内切核酸酶(FEN1),胰岛素样生长因子结合蛋白6(IGFBP6),胰岛素等六个新型抗体/抗原复合物进行了验证。像RA患者中的生长因子I(IGF1)和斯坦钙钙蛋白2(STC2))还鉴定了瓜氨酸化MBP的免疫优势表位。鉴定出的生物标志物具有很高的特异性,尤其是MBP。

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