抗半乳糖醛酸聚糖(PGA)抗体在诱导类风湿关节炎骨侵蚀中的作用

类风湿关节炎（RA）是以慢性侵蚀性关节炎为主要表现的自身免疫病, 破骨细胞过度活化导致的骨侵蚀是RA的主要病理特征和致残原因，但目前诱导破骨细胞活化的机制还不完全清楚。本课题组前期工作中发现了一种新的自身抗体-半乳糖醛酸聚糖（PGA）抗体，该抗体可能在RA相关的破骨细胞活化中发挥关键作用。我们发现，PGA抗体只在RA病人存在而健康人几乎无法检出，用于诊断RA的敏感和特异性均优于现行指标抗环瓜氨酸肽CCP及类风湿因子RF，且抗体水平与骨吸收指标呈正相关。更重要的是，PGA抗体可以直接诱导动物发生关节炎，体外培养能促进破骨细胞分化和释放组织蛋白酶，提示PGA抗体对关节炎骨侵蚀有致病作用。本项目将在前期基础上，利用体外破骨细胞培养、体内关节炎模型和病人血清学检测，明确PGA抗体在骨侵蚀中的致病作用，探讨PGA抗体活化破骨细胞的分子机制。本项目有可能为RA早期诊断提供新标志物，为治疗提供新的靶点。

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic erosive arthritis. Bone erosion caused by excessive activation of osteoclasts is the main pathological feature and disability cause of RA. However, the mechanism of inducing osteoclast activation is still unclear. In our previous work, we found a new autoantibody –polygalacturonic acid (PGA) antibody, which may play a key role in RA-related osteoclast activation. We found that PGA antibody only existed in patients with RA and could hardly be detected in healthy people. The sensitivity and specificity of PGA antibody in the diagnosis of RA were better than those of CCP and RF, and the level of PGA antibody was positively correlated with bone resorption index. More importantly, PGA antibody can directly induce arthritis in animals. In vitro culture, PGA antibody can promote osteoclast differentiation and cathepsin releasing, suggesting that PGA antibody has pathogenic effect on osteoarthritis bone erosion. On the basis of previous studies, this project will clarify the pathogenic role of PGA antibody in bone erosion by using osteoclast culture in vitro, arthritis model in vivo and serological detection of patients, and explore the molecular mechanism of PGA antibody activating osteoclasts. This project may provide new markers for early diagnosis of RA and new targets for treatment.