Role of anti-Type II collagen antibody formation in pathogenesis of rheumatoid arthritis.

为了阐明自身胶原免疫在类风湿关节炎(RA)发病机制中的作用，我们建立了一种改进的抗胶原抗体的酶联免疫吸附试验(ELISA)，以减少非特异性背景干扰并提供更高的灵敏度。在该检测系统的基础上，发现RA患者的抗胶原抗体是针对II型胶原的，与I型和III型胶原没有交叉反应。RA血清识别的主要抗原决定簇位于人II型胶原分子的溴化氰多肽(CB)11和CB-8所代表的区域。提示类风湿关节炎患者的抗胶原抗体来源于II型胶原分子构象决定因素。此外，在RA患者的关节软骨中也发现了抗II型胶原抗体，很可能与关节破坏的发病机制有关。因此，本研究有力地提示类风湿关节炎患者抗胶原抗体的形成可能不是结缔组织破坏的结果。尽管天然II型胶原RA自身免疫发展的刺激因素尚不清楚，但这种免疫在发病时似乎在功能上是活跃的，并在疾病的慢性持久发展中发挥着重要作用。

In order to clarity the role of autoimmunity to collagen in the pathogenesis of rheumatoid arthritis(RA), we have developed an improved enzyme-linked immunosorbent assay (ELISA) for anti-collagen antibodies to diminish non-specific background interference and provide higher sensitivity. Based on this assay system, it was found that anti-collagen antibodies in RA patients are specific to Type II collagen and have no cross-reactivity with Type I and Type III collagens. The major antigenic determinants which are recognized by RA sera were found to reside in the region represented by cyanogen bromide peptide (CB) 11and CB-8 of human Type II collagen molecule. The result indicate that anti-collagen antibodies in RA patients are derived from the conformational determinants of Type II collagen molecule. Also, anti-Type II collagen antibodies were found in the articular cartilage of RA patients,and are most likely to contribute to the pathogenesis of joint destruction. Thus, the present study strongly indicate that the formation of anti-collagen anti-bodies in RA may not be the consequence of the destruction of the connective tissues. Although the stimulus for the development of autoimmunity to native Type II colagen RA remains unknown, the immunization seems to be functionally active at the onset and to play an important role for chronic perpetuation of the disease.