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首页> 外文期刊>Nature immunology >Autoantibodies to GPI in rheumatoid arthritis: linkage between an animal model and human disease
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Autoantibodies to GPI in rheumatoid arthritis: linkage between an animal model and human disease

机译：类风湿关节炎中针对GPI的自身抗体：动物模型与人类疾病之间的联系

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摘要

In K/BxN T cell receptor-transgenic mice, spontaneous inflammatory arthritis exhibiting many of the features of human rheumatoid arthritis (RA) is initiated by T cells, but is almost entirely sustained by antibodies to the self-antigen glucose-6-phosphate isomerase (GPI). The relevance of these observations to human disease has been questioned. Here we show that 64% of humans with RA, but not controls, had increased concentrations of anti-GPI immunoglobulin G (IgG) in serum and synovial fluid. In addition, the concentrations of soluble GPI in the sera and synovial fluids of RA patients were also elevated, which led to immune complex formation. Using phage-display methods, we cloned a panel of specific high-affinity human monoclonal anti-GPI IgGs from patient with RA. These antibodies were highly somatically mutated, which was indicative of an affinity-matured response that was antigen driven. Immunohistochemistry of RA synovium showed high concentrations of GPI on the surface of the synovial lining and on the endothelial cell surface of arterioles; this indicated a mechanism by which antibodies to GPI may precipitate joint disease. The results indicate that the immunological events that lead to the development of autoimmune disease in the K/BxN mouse model may also occur in human RA. This data may be sued to develop new strategies for therapeutic intervention.
机译：在K / BxN T细胞受体转基因小鼠中，表现出人类类风湿性关节炎（RA）许多特征的自发性炎症性关节炎是由T细胞引发的，但几乎完全由自身抗原葡萄糖-6-磷酸异构酶的抗体所维持（GPI）。这些观察与人类疾病的相关性受到质疑。在这里，我们显示有RA而非对照的64％的人血清和滑液中抗GPI免疫球蛋白G（IgG）的浓度增加。另外，RA患者的血清和滑液中可溶性GPI的浓度也升高，这导致免疫复合物的形成。使用噬菌体展示方法，我们从RA患者中克隆了一组特异性高亲和力的人单克隆抗GPI IgG。这些抗体是高度体细胞突变的，这表明是抗原驱动的亲和力成熟的应答。 RA滑膜的免疫组织化学结果显示，滑膜内膜表面和小动脉内皮细胞表面GPI浓度较高。这表明了针对GPI的抗体可能导致关节疾病的机制。结果表明，导致人自身免疫疾病在K / BxN小鼠模型中发展的免疫学事件也可能在人RA中发生。可以使用该数据来开发治疗干预的新策略。

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