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Abstract：
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Many patients carry anti-citrullinated protein autoantibodies (ACPA). Overactivation of the complement system seems to be part of the pathogenesis of RA, and autoantibodies against the pathway initiators C1q and MBL, and the regulator of the complement alternative pathway, factor H (FH), were previously reported. Our aim was to analyze the presence and role of autoantibodies against complement proteins in a Hungarian RA cohort. To this end, serum samples of 97 ACPA-positive RA patients and 117 healthy controls were analyzed for autoantibodies against FH, factor B (FB), C3b, C3-convertase (C3bBbP), C1q, MBL and factor I. In this cohort, we did not detect any patient with FH autoantibodies but detected C1q autoantibodies in four patients, MBL autoantibodies in two patients and FB autoantibodies in five patients. Since the latter autoantibodies were previously reported in patients with kidney diseases but not in RA, we set out to further characterize such FB autoantibodies. The isotypes of the analyzed autoantibodies were IgG2, IgG3, IgGκ, IgGλ and their binding site was localized in the Bb part of FB. We detected in vivo formed FB-autoanti-FB complexes by Western blot. The effect of the autoantibodies on the formation, activity and FH-mediated decay of the C3 convertase in solid phase convertase assays was determined. In order to investigate the effect of the autoantibodies on complement functions, hemolysis assays and fluid phase complement activation assays were performed. The autoantibodies partially inhibited the complement-mediated hemolysis of rabbit red blood cells, inhibited the activity of the solid phase C3-convertase and C3 and C5b-9 deposition on complement activating surfaces. In summary, in ACPA-positive RA patients we identified FB autoantibodies. The characterized FB autoantibodies did not enhance complement activation, rather, they had inhibitory effect on complement. These results support the involvement of the complement system in the pathomechanism of RA and raise the possibility that protective autoantibodies may be generated in some patients against the alternative pathway C3 convertase. However, further analyses are needed to assess the exact role of such autoantibodies.
摘要：
类风湿性关节炎（RA）是一种影响关节的慢性炎症性自身免疫性疾病。许多患者携带抗瓜氨酸化蛋白自身抗体(ACPA)。补体系统的过度激活似乎是RA发病机制的一部分，以及针对途径引发剂C1q和MBL的自身抗体，以及补体旁路的调节因子,系数H(FH),以前报道过。我们的目的是分析匈牙利RA队列中针对补体蛋白的自身抗体的存在和作用。为此,对97例ACPA阳性RA患者和117例健康对照的血清样本进行抗FH自身抗体分析,系数B(FB)，C3b,C3-转化酶(C3bBbP),C1q,MBL和因子I。在这个队列中，我们没有检测到任何FH自身抗体的患者，但在4例患者中检测到C1q自身抗体，2例患者的MBL自身抗体和5例患者的FB自身抗体。由于后者的自身抗体以前是在肾脏疾病患者中报道的，但在RA中没有报道，我们着手进一步表征此类FB自身抗体。分析的自身抗体的同种型是IgG2，IgG3，IgGκ，IgGλ及其结合位点位于FB的Bb部分。我们通过Western印迹检测了体内形成的FB-自体抗FB复合物。自身抗体对地层的影响，测定了固相转化酶测定中C3转化酶的活性和FH介导的衰变。为了研究自身抗体对补体功能的影响，进行溶血测定和液相补体激活测定。自身抗体部分抑制补体介导的兔红细胞溶血,抑制固相C3转化酶的活性以及C3和C5b-9在补体激活表面上的沉积。总之,在ACPA阳性RA患者中,我们鉴定了FB自身抗体.表征的FB自身抗体没有增强补体激活，更确切地说,它们对补体有抑制作用。这些结果支持补体系统参与RA的病理机制，并提高了在某些患者中可能产生针对替代途径C3转化酶的保护性自身抗体的可能性。然而,需要进一步分析以评估此类自身抗体的确切作用.
