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

抗 II 型胶原抗体形成在类风湿性关节炎发病机制中的作用。

• 批准号: 03670715
• 负责人: FUJII Katsuyuki
• 金额: $ 1.28万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670715/
• 关键词: rheumatoid arhtritis; Type II collagen; anti-Type II collagen antibodies; autoimmunity; 漫性関節リウマチ; 抗II型コラーゲン; 抗II型コラ-ゲン抗体; 自己抗体

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.

为了阐明胶原自身免疫在类风湿关节炎（RA）发病机制中的作用，我们建立了一种改良的抗胶原抗体酶联免疫吸附试验（ELISA），以减少非特异性背景干扰，提高灵敏度。基于该检测系统，发现RA患者中的抗胶原抗体对II型胶原具有特异性，并且与I型和III型胶原没有交叉反应性。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肽（CB）11和CB-8所代表的区域。结果表明，RA患者的抗胶原抗体来源于II型胶原分子的构象决定簇。此外，在RA患者的关节软骨中发现了抗II型胶原抗体，并且最有可能导致关节破坏的发病机制。因此，本研究强烈表明，抗胶原抗体的形成在RA可能不是结缔组织的破坏的结果。虽然刺激天然II型胶原RA自身免疫的发展仍然未知，免疫似乎是在发病时功能活跃，并发挥了重要作用的慢性延续的疾病。

项目成果

藤井 克之: "RA患者の抗II型コラーゲン抗体" 関節外科. 10. 281-289 (1991)

Katsuyuki Fujii：“RA 患者中的抗 II 型胶原抗体”关节外科。 10. 281-289 (1991)

Katsuyuki Fujii: "The diagnostic significan of anti-TypeIIclollagen antibody assay in rheumatoid arthritis" Int、 Orthop.16. 272-276 (1992)

Katsuyuki Fujii：“抗 II 型胶原蛋白抗体测定在类风湿性关节炎中的诊断意义”Int，Orthop.16 (1992)。

藤井 克之: "慢性関節リウマチと抗コラーゲン抗体" リウマチ科. 5. 358-366 (1991)

Katsuyuki Fujii：“慢性类风湿性关节炎和抗胶原抗体”风湿病学。5. 358-366 (1991)

藤井 克之: "慢性関節リウマチと抗II型コラーゲン抗体" リウマチ科. 5. 358-366 (1991)

Katsuyuki Fujii：“慢性类风湿性关节炎和抗 II 型胶原抗体”风湿病学。 5. 358-366 (1991)

Katsuyuki Fujii: "The diagnostic significance of anti-TypeII collagen antibody assay in rheumatoid arthritis" Int.Orthop.16. 272-276 (1992)

Katsuyuki Fujii：“抗 II 型胶原蛋白抗体测定在类风湿性关节炎中的诊断意义”Int.Orthop.16。