Synovial Epstein‐Barr virus infection increases the risk of rheumatoid arthritis in individuals with the shared HLA–DR4 epitope

Objective To investigate the presence of the Epstein-Barr virus (EBV) in rheumatoid arthritis (RA) synovium and its correlation with the HLA genotype in an attempt to elucidate the role of EBV in the pathogenesis of RA. Methods EBV DNA/RNA was investigated by polymerase chain reaction (PCR) analysis of synovial tissue from 84 patients with RA and from 81 patients with non-RA arthritis (controls) and was correlated with the patients' HLA genotype. Results EBV DNA and EBV-encoded RNA 1 transcripts were significantly more frequently present in synovial tissue from the RA patients (29 of 84) than in that from the non-RA patient controls (8 of 81). EBV DNA–positive individuals had a 5.47 times higher risk of presenting with RA than did EBV DNA–negative individuals. In HLA–DRB1*0401,0404,0405,0408–positive or shared epitope–positive patients, the risk was further increased (odds ratio for EBV and HLA–DR4 ∼41, for EBV and the shared epitope ∼15) compared with those who lacked both EBV DNA and RA-linked HLA genotypes. Conclusion EBV seems to function as an environmental risk factor for RA, particularly in patients with the RA-linked HLA–DRB1 alleles.