Lytic Epstein‐Barr virus infection in the synovial tissue of patients with rheumatoid arthritis

Objective To evaluate the existence of Epstein-Barr virus (EBV) infection in the synovial tissue of patients with rheumatoid arthritis (RA). Methods Synovial tissues were obtained at synovectomy or arthroplasty from 32 patients with RA and 30 control patients with osteoarthritis (OA). EBV DNA was detected by Southern blot hybridization and/or polymerase chain reaction (PCR) amplification. To localize the EBV-infected cells, tissue sections were studied by RNA in situ hybridization (ISH) for the EBV-encoded small RNA 1 (EBER-1), by DNA ISH for the Bam HI W region of EBV DNA, and by immunohistochemistry for EBV lytic proteins BZLF1 and gp350/220. Results EBV DNA was detected by PCR in 15 of the 32 samples from RA patients (47%), but in none of those from the 30 OA patients (P 1 EBV copy/1,000 cells (referred to as EBV 2+), and 6 contained 1 copy/1,000–5,000 cells (EBV 1+). Among the 9 EBV 2+ samples, 3 were also positive for EBV DNA by Southern blot hybridization, 5 were positive for EBER-1 by RNA ISH, and 3 were positive for EBV DNA by DNA ISH. Immunohistochemical analysis showed positive signals in all samples for BZLF1 and in 7 samples for gp350/220. In each examination, the positive signals were detected not only in lymphocytes, but also in synovial lining cells. Conclusion EBV was frequently detected in the synovial tissue of RA patients. The infected cells were both lymphocytes and synovial cells, and expressed EBV proteins associated with virus replication. These findings suggest that EBV may play a role in the pathogenesis of RA.