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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。
The pathogenesis of rheumatoid arthritis (RA) is not yet clear, but genetic and environmental factors play an important role in the pathogenesis of RA. In recent thirty years, the relationship between the pathogenesis of RA and Epstein-Barr virus (EBV) infection has become a research hotspot. Many literatures show that the titer of EBV antibody in patients with RA is higher than that of the normal control group. Antibodies against citrullinated EBV peptide are also present in serum. However, lymphocytes in RA patients show immunoreactivity in response to EBV. The use of PCR, in situ hybridization and immunohistochemical techniques found that RA synovial EBV antibodies and genetic material also exists, although some of the results are still inconsistent. Some EBV antibodies share amino acid sequence homology with their own tissues and cells, such as QKRAARA, which is homologous to HLA-DRB1 * 0401/0405 and EBV gp110 glycoprotein. Based on the above evidence, it is suggested that EBV may mediate the pathogenesis of RA through the “molecular mimicry” mechanism. In addition, aberrant signaling pathways of SAP (signaling lymphatic activation molecule-associated protein) may also be one of the molecular biological mechanisms by which EBV leads to the development of RA. Although there are many links between EBV and RA, more experimental evidence needs to be provided to clarify their causal relationship. To reveal the immunological nature of RA and EBV infection is of great scientific significance for clinical prevention and treatment of RA.