钙网织蛋白在类风湿关节炎患者体内表达上调及其意义

Up-regulation of calreticulin expression and its significance in patients with rheumatoid arthritis in vivo

目的通过分析钙网织蛋白（CRT）在类风湿关节炎（RA）患者体内的表达水平，进一步探讨CRT在RA发病机制中的作用。方法采用酶联免疫吸附试验（ELISA）法检测活动期RA、骨关节炎、系统性红斑狼疮（sLE）、其他自身免疫性疾病和健康对照组（HC）血清及RA和骨关节炎滑液中CRT的含量，蛋白印迹法分析血清中CRT的存在形式，病理学方法检测CRT在RA和骨关节炎关节滑膜组织中的表达。采用单因素方差分析、SNK．q检验进行统计分析。结果RA组血清中CRT含量[（4．8±2．4）ng／ml]高于骨关节炎组[（3．6±0．9）ng／ml]、SLE组[4．0±1．5）ng／ml]、其他自身免疫性疾病组[（3．9±0．8）。g／ml]以及健康对照组[（3．7±0．6）ng／ml]，差异有统计学意义（P〈0．05）。RA组与骨关节炎组滑液中CRT含量差异无统计学意义。CRT在血清中仅存在单体一种形式。RA滑膜组织中可见大量炎性细胞浸润，CRT呈现高表达，主要位于滑膜组织的衬里层和衬里下层、血管内皮细胞以及血管周围；在骨关节炎，CRT仅在衬里层及血管周围有极少量的表达。结论RA血清中CRT含量明显增高，在滑膜组织中呈高表达，且表达位置不同于骨关节炎。提示CRT可能参与了RA的关节炎症反应及血管翳的形成。

Objective To investigate the role of calreticulin （CRT） in the pathogenesis of rheumatoid arthritis （RA） by analyzing its expression in the sera, synovial fluid and synovial membrane in patients with RA. Methods Levels of CRT in the sera from patients with RA, osteoarthritis （OA）, systemic lupus erythematosus （SLE）, other autoimmune diseases and health control （HC） were detected by enzyme linked immunosorbent assay （ELISA） and Western bloting. CRT leyels in synovial fluid from RA and OA patients were measured by ELISA. Pathological methods were employed to analyze the expression and localization of CRT in synovial membrane. ANVOA, SNK-q test were used for statistical analysis. Results CRT was found to be significantly up-regnlated in sera from RA [（4.8~2.4） ng/ml] than that from in OA [（3.6~0.9） ng/ml], SEE [（4.0~1.5） ng/ml], other autoimmune diseases [（3.9~0.8） ng/ml] and HC [（3.7~0.6） ng/ml]. Only the monomer form of CRT in the serum could be detected. Pathological results showed that in RA synovium, CRT was mainly expressed in the lining and sublining layers, endothelial cells and perivascular areas; while in OA, only few CRT staining was seen in perivaseular areas and the synovial lines. Conclusion In RA, increased levels of CRT are detected in the sera. In addition, high expression of CRT is observed in synovium and its distribution are different from OA. Our results suggest that CRT may be involved in RA joint inflammation and pannus formation. CRT may become a potential serological marker in the diagnosis of RA.