类风湿关节炎患者关节损伤相关因子和EBV抗体检测的意义

Implication for the detection of the joint lesion associated factors and Epstein-Barr virus antibodies in patients with rheumatoid arthritis

分析类风湿关节炎(rheumatoid arthritis,RA)患者关节损伤因子和EB病毒(Epstein-Barr virus,EBV)抗体检测的意义,探索RA发病与EBV感染的关系。采用高敏感性ELISA试剂盒与[3H]-TdR掺入实验,检测和分析RA患者关节损伤相关因子胶原Ⅱ抗体(CⅡ抗体)、MMP-3和TI MP-1的表达水平,同时,检测与分析患者自身反应性T细胞对EBV相关肽段的免疫应答和EBV抗体的表达格局。检测结果表明,SF中CⅡ的IgG抗体在RA患者与OA患者两组之间具有统计学差异(P<0.05);同时,RA患者SF中检测到关节损伤因子MMP-3和TI MP-1,两者均显著高于血清(P<0.001),而SF组中MMP-3∶TI MP-1比值同血清组相比也具有显著的统计学差异(P<0.001)。重要的是,多数RA患者被检出EBVgp110、EBV-EBNA-1(IgG)、EBV-VCA(IgG)抗体,且来自RA患者的自身T细胞对合成的EBV gp110肽段呈现更为显著的自身反应性(P<0.001)。RA患者检出的CⅡ抗体、MMP-3和TI MP-1的异常表达可能与患者的EBV感染有关。本文的实验结果提示抗病毒和免疫调节可能是临床免疫干预和治疗RA的思路之一。

To analyze the implication for the detection of the joint lesion associated factors and Epstein-Barr virus（EBV） antibodies in patients with rheumatoid arthritis（RA） so as to explore the relationship between pathogenesis of RA and EBV infection,the expression levels of anti-EBV antibodies and anti-collagen Ⅱ（CⅡ） antibodies,joint lesion associated factor MMP-3 and TIMP-1 were detected by high sensitive ELISA,while clonal expansion of RA self-reactive T cells induced by synthesized EBV peptides was analyzed by 3H-TdR incorporation analysis.The experimental results showed that the anti-collagen Ⅱ antibodies were found both in serum and synovial fluid（SF） of RA patients,while in SF,the level of IgG antibodies in RA patients was significantly higher than that in the OA control of patients（P0.01）.The levels of joint lesion associated factors MMP-3 and TIMP-1 in SP of RA patients were both higher than those in serum of RA patients（P0.001）,but in comparison with the serum group,the MMP-3/TIMP-1 ratio in the SF group showed significant difference（P0.001）.Moreover,the anti-EBV gp110 antibodies were detected in most of RA SF and peripheral blood of RA patients,other anti-EBV antibodies.Such as EBV-VCA IgM,EBV-EBNA-1 IgG,EBV-VCA IgG,and anti-EBV-EBNA-1 IgG were also detected.The self reactive T cells from RA patients were found to have marked auto-reactivity to synthesized EBV gp110 peptide.From these experimental results,it is concluded that the EBV infection has some relationship with abnormal clonal expasion of T/B cells in RA patients,especially the abnormal high levels of MMP-3,TIMP-1 and anti-CⅡ antibodies.Possibly,these abnormality may be caused by the mechanism of ＂moleculat mimicry＂,the self-reactive cells in RA patients may cross-react with EBV and self peptides during the course of viral infection,and then lead to the self-tissue destruction and finally cause activation and development of RA.Our experimental results suggest that anti-virus therapy and immunoregulation may be one of the new idea for the prevention and treatment of rheumatoid arthritis.