Seroepidemiological study of relationships between Epstein-Barr virus and rheumatoid arthritis.

Abstract

A B S T R A C T To elucidate the relationship between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA), we measured antibodies to RA-associated nuclear antigen (anti-RANA) and three other EBV-related antigens in the sera of RA patients and controls. Our study groups consisted of 89 patients with definite or classical RA, mean age 56, male/female ratio 47:42; and 53 normal and osteoarthritis controls, mean age 51, male/female ratio 25:28. In addition to anti-RANA, we measured antibodies to viral capsid antigen (anti-VCA), early antigen (anti-EA) and EBV-associated nuclear antigen (anti-EBNA).Anti-RANA was detected in 71% of RA patients but in only 6% of controls. Elevated anti-VCA titers (>1: 160) were more common in RA patients than controls, 31% compared with 15%. The geometric mean titer of anti-VCA was significantly higher in the RA group, 133 compared with 58. Anti-EA was present in 53% of RA patients but only 19% of controls. Anti-EA in elevated titers (>1:20) was present in 26% of RA patients but only 7% of controls. Characterization of the anti-EA antibodies revealed that the RA patients reacted primarily with the diffuse component, whereas the majority of the controls reacted with the restricted component ofthe EA complex. In contrast, the frequencies, distributions, and geometric mean titers of anti-EBNA were not significantly different between the two groups. Correlative analysis ofthese antibodies showed highly significant relationships between anti-VCA and anti-EA, and anti-RANA and anti-EBNA in the RA group. These data are compatible with the interpretation that RA patients have either more active EBV infections than controls or an altered regulation of their immune response to this infectious agent.

Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen.

“…Antibody responses against particular antigenic regions of EBNA-I might not be detectable in immunofluorescence assays. Also, preferential responses against particular antigenic regions of EBNA-I may be responsible for increased anti-RANA (RA nuclear antigen) antibody titers in RA patients (47), since the RANA epitope appears to reside on the EBNA-I molecule (31). Further studies on antibody and T cell responses ofRA patients early in the course ofdisease will be required to determine the potential importance of crossreactive antigens in pathogenesis.…”

Rheumatoid Factors Induce Signaling from B Cells, Leading to Epstein-Barr Virus and B-Cell Activation

“…RA patients have a higher frequency and/or higher levels of antibodies to EBV in serum than do normal individuals (1,7,11,30). It has been reported that the number of circulating B cells infected with EBV is increased in RA patients (36).…”

The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders — Similarities and differences

“…The titers of antibodies against EBNA, the nuclear antigens of EBV are higher in patients with RA than in healthy controls [69]. 2.…”