EBV感染与类风湿性关节炎发病机制关联性的研究进展  

The Relevance between RA Pathogenesis and EBV Infection

作　　者：黄秋愉[1] 张冬青[1] 

机构地区：[1]上海交通大学医学院上海市免疫学研究所,上海200025

出　　处：《中国细胞生物学学报》2010年第5期771-776,共6页Chinese Journal of Cell Biology

基　　金：国家自然科学基金项目(No.30471593);上海市科委重点项目(No.07JC14033);上海市免疫学研究所项目(No.08-A04)资助项目~~

摘　　要：类风湿性关节炎(Rheumatoid Arthritis,RA)的发病机制尚未明确,但遗传因素和环境因素在RA的发病中起着重要作用。近三十年来,RA的发病机制与EBV(Epstein-Barr virus,又称HHV-4)感染的关联性已成为研究热点。诸多文献表明,RA患者的EBV抗体滴度高于正常对照组,血清中还存在着抗瓜氨酸化EBV肽的抗体,而RA患者体内的淋巴细胞却对EBV的应答呈现免疫低反应性。采用PCR、原位杂交和免疫组化等技术发现RA患者滑膜同样存在着EBV抗体及遗传物质,尽管有些研究结果仍不一致。一些EBV抗体与患者自身组织和细胞间存在氨基酸序列的同源性,如HLA-DRB1*0401/0405与EBV gp110糖蛋白存在同源序列的QKRAARA。基于上述证据提示EBV可能通过"分子模拟(molecular mimicry)"机制介导了RA的发病。另外,SAP(signallinglymphocyte activation molecule-associated protein,信号淋巴细胞活化分子相关蛋白)信号途径的异常可能也是EBV导致RA发生发展的分子生物学机制之一。尽管EBV同RA之间存在着诸多的联系,但仍需提供更多的实验证据阐明它们的因果关系。揭示RA发病与EBV感染的免疫学本质对临床防治RA有着十分重要的科学意义。Though the pathogenesis of RA is still puzzling,the relevance between RA pathogenesis and EBV （Epstein-Barr virus,HHV-4） infection has recently become a research hot spot.Documents have shown that, comparing to healthy controls,the RA are characterized by high titers of anti-EBV antibodies,anti-CCP antibodies and impaired T-cell responses to EBV antigens.In situ hybridization,immuno-histochemical and PCR techniques have identified EBV antigens and genetic material within the rheumatoid synovium,albeit with variable results.There are some similarities of amino acid sequences between anti-EBV antibodies and self antigens,such as the homologous sequence QKRAARA existed in both HLA-DRB1＊040110405 and EBV gp110 protein.Molecular mimicry is assumed to occur during the initiation and the process of RA induced by EBV.Several evidences indicated the impairment of the SAP（signalling lymphocyte activation molecule-associated protein） signal path might be the molecular biological mechanisms of pathogenesis in RA.Despite these multiple and complex links between EBV and RA,proofs of research are still needed to illuminate the causal association.For the illumination of the immunological relevance is of great benefit to clinical treatment in RA.

关 键 词：类风湿性关节炎(RA) EBV 分子模拟 自身免疫病 免疫应答 

分 类 号：R593.22[医药卫生—内科学]