Background/Purpose: Epstein-Barr virus (EBV) infection causes various malignant tumors such as B cell lymphoma and epithelial cell cancer. Previous reports showed several variants in carboxyl-terminal region of EBV nuclear antigen 1 (EBNA-1), and the mutation was frequently detected in patients with nasopharyngeal carcinoma. The mutation of EBV gene may trigger development of the malignant cells. It was reported that titer of anti-EBV antibody was higher in rheumatoid arthritis (RA) compared to controls. Interestingly, the protein sequence of EBV gp110 glycoprotein resembles HLA DRB1 shared epitope (SE). These data suggest EBV infection may play a role of RA, however, underlying mechanisms remains unknown. Moreover, mutation of EBV in RA patients has not been examined. We then investigated EBNA-1 carboxy-terminal region in the synovial tissue of RA.

Methods: One hundred twenty-eight RA and 98 osteoarthritis (OA) patients undergoing joint surgery of the knee at the Toho University Omori Medical Center were enrolled in this study. Synovial tissues were collected during surgery under sterile condition. Informed consent was obtained from all the patients. DNA was extracted from the synovial tissues. The EBV gene was determined by nested PCR for amplifying EBNA-1 carboxy-terminal region, and then, the amplicons were detected by performing electrophoresis. Nucleotide sequence of the PCR product was determined. HLA DRB1 genotyping was also performed.

Results: EBV DNA was more frequently detected in synovial tissue from RA patients (32.8%; 42 of 128) than OA patient (15.3%; 15 of 98) (p<0.01, chi-squared test). The sequence of EBNA-1 carboxy-terminal revealed Japanese prototype (V-Val subtype) in 35 of the 42 RA (83.3%) and 13 of the 15 OA (86.7%) patients. Although four other subtypes were also detected in small number of patients, there were no significant differences between RA and OA. Frequency of HLA-DRB1*0405, *0410, *1001 (SE) was significantly higher in RA (55.5%) than OA (30.6%). Proportion of EBV-positive tended to be higher in SE-positive (39.4%; 28 of 71) than SE-negative (24.6%; 14 of 57), although it is not statistically significant.

Conclusion:

EBV infection might be an environmental risk factor for development or chronic synovitis of RA. However, nucleotide mutations of EBNA-1 may not contribute it.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/epstein-barr-virus-infection-and-epstein-barr-virus%e3%80%80nuclear-antigen-1-variants-in-the-synovial-tissue-of-rheumatoid-arthritis/