Foltyn Zadura Anna, Zipfel Peter F, Bokarewa Maria I, Sturfelt Gunnar, Jönsen Andreas, Nilsson Sara C, Hillarp Andreas, Saxne Tore, Trouw Leendert A, Blom Anna M
Arthritis Res Ther. 2012 Aug 15;14(4):R185. doi: 10.1186/ar4016.
Complement activation is involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS). Autoantibodies to complement inhibitor factor H (FH), particularly in association with deletions of the gene coding for FH-related protein 1 (CFHR1), are associated with aHUS.
Autoantibodies against FH, factor I (FI) and C4b-binding protein (C4BP) were measured by ELISA, while CFHR1 homozygous deletion was determined with Western blotting of sera. Epitopes for FH autoantibodies were mapped using recombinant fragments of FH.
FH autoantibodies were detected in SLE (6.7%, n = 60, RA patients (16.5%, n = 97 in the Swedish cohort and 9.2%, n = 217 in the Dutch cohort) and thrombosis patients positive for the lupus anticoagulants (LA+) test (9.4%, n = 64) compared with aHUS patients (11.7%, n = 103). In the control groups (n = 354), an average of 4% of individuals were positive for FH autoantibodies. The frequencies observed in both RA cohorts and LA+ patients were statistically significantly higher than in controls. We also found that an average of 15.2% of the FH-autoantibody positive individuals in all studied disease groups had homozygous deficiency of CFHR1 compared with 3.8% of the FH autoantibody negative patients. The levels of FH autoantibodies varied in individual patients over time. FH autoantibodies found in LA+, SLE and RA were directed against several epitopes across FH in contrast to those found in aHUS, which bound mainly to the C-terminus. Autoantibodies against FI and C4BP were detected in some patients and controls but they were not associated with any of the diseases analyzed in this study.
Autoantibodies against FH are not specific for aHUS but are present at a significant frequency in rheumatic diseases where they could be involved in pathophysiological mechanisms.
补体激活参与类风湿关节炎（RA）、系统性红斑狼疮（SLE）和非典型溶血尿毒综合征（aHUS）。针对补体抑制因子H（FH）的自身抗体，尤其是与编码FH相关蛋白1（CFHR1）的基因缺失相关的自身抗体，与aHUS有关。
采用酶联免疫吸附测定法（ELISA）检测针对FH、因子I（FI）和C4b结合蛋白（C4BP）的自身抗体，同时通过血清蛋白质印迹法确定CFHR1纯合缺失情况。使用FH重组片段绘制FH自身抗体的表位。
在SLE患者中检测到FH自身抗体的比例为6.7%（n = 60），RA患者中瑞典队列的比例为16.5%（n = 97），荷兰队列的比例为9.2%（n = 217），狼疮抗凝物（LA+）检测呈阳性的血栓形成患者中的比例为9.4%（n = 64），而aHUS患者中的比例为11.7%（n = 103）。在对照组（n = 354）中，平均4%的个体FH自身抗体呈阳性。在两个RA队列和LA+患者中观察到的频率在统计学上显著高于对照组。我们还发现，在所有研究疾病组中，平均15.2%的FH自身抗体阳性个体存在CFHR1纯合缺陷，而FH自身抗体阴性患者的这一比例为3.8%。个体患者中FH自身抗体水平随时间变化。与主要结合C端的aHUS患者中发现的FH自身抗体不同，在LA+、SLE和RA患者中发现的FH自身抗体针对FH的多个表位。在一些患者和对照组中检测到针对FI和C4BP的自身抗体，但它们与本研究分析的任何疾病均无关联。
针对FH的自身抗体并非aHUS所特有，而是在风湿性疾病中以显著频率存在，可能参与病理生理机制。
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