Epstein-Barr virus infection in peripheral blood mononuclear cells, synovial fluid cells, and synovial membranes of patients with rheumatoid arthritis

Objective. Different infectious agents have been proposed to be involved in the pathogenesis of rheumatoid arthritis (RA). We investigated the role of latent Epstein-Barr virus (EBV) infection in patients with RA. Methods. Sera of 55 patients with RA and 60 age and sex matched healthy con trols were examined for antibodies against EBV encoded antigens (EBNA-1, VC A, and EA) by ELISA. The presence of viral DNA was analyzed by polymerase c hain amplification of DNA isolated from peripheral blood mononuclear cells (PBMC) of: these samples and from cells of synovial fluid (SF) specimens. P araffin sections of synovial membranes from 25 patients were subjected to i n situ hybridization analysis for the EBV encoded small RNA EBER1 and EBER2 , Results, Two-fold increased values of IgG antibodies against EBNA-1 were fo und in patients with RA in comparison to healthy controls (p = 0.029), No s tatistically significant difference could be observed for antibody levels a gainst EBV-VCA. Fourteen (24.1%) of 55 patients with RA had serological evi dence of reactivated EBV infection in comparison to none of the control gro up (p = 0.028). In PBMC, EBV DNA was detected in a significantly higher pro portion in the patient group (50.9 vs 30%; p = 0.02). In addition, SF cells harbored the viral DNA in 30% of RA cases compared to 16.6% of control cas es (p = 0.02). However, EBER1/2 transcripts could only be Found within syno vial membranes of 2 (8%) of 25 patients with RA. Conclusion. These findings support the hypothesis that EBV infection may be involved in the pathogenesis of RA, Further studies may define the precise pathogenetic mechanisms of viral infection for the development of inflamma tory arthritis.