New findings suggest that immune responses to Epstein–Barr virus (EBV) may be associated with heightened autoimmunity in rheumatoid arthritis (RA). In a retrospective observational study, patients with RA who tested positive for anti-EBV early antigen diffuse and restricted type (EA-DR) immunoglobulin G (IgG) antibodies showed higher levels of disease activity and autoantibody production than antibody-negative patients.
Evaluating EBV Markers in RA
The study examined 70 patients receiving treatment for RA, comparing clinical and laboratory characteristics between those who tested positive and negative for anti-EBV EA-DR IgG antibodies. Overall, 30 patients were antibody-positive, corresponding to a positivity rate of 43.9%.
Among the antibody-positive group, EBV DNA polymerase chain reaction testing was performed in 18 patients, with 14 showing detectable EBV DNA. This finding supports ongoing or recent viral activity in a substantial proportion of EBV-seropositive RA patients.
Associations With Disease Activity and Autoantibodies
Univariate analysis demonstrated that patients positive for anti-EBV EA-DR IgG antibodies had significantly higher disease activity scores based on the Disease Activity Score in 28 joints with C-reactive protein. These patients also exhibited increased peripheral blood lymphocyte counts, higher anti-cyclic citrullinated peptide antibody (ACPA) levels, and elevated rheumatoid factor titres compared with antibody-negative patients.
In multivariate analysis, peripheral blood lymphocyte count and ACPA levels remained independently associated with anti-EBV EA-DR IgG positivity. Notably, ACPA levels were significantly higher in EBV antibody–positive patients, reinforcing a link between EBV-related immune responses and RA-specific autoantibody production.
Implications for RA Pathophysiology
These findings add to accumulating evidence implicating EBV in the immunological landscape of RA. While EBV infection is widespread in the general population, differential immune responses to viral antigens may contribute to disease activity or severity in RA through mechanisms related to B-cell activation and autoantibody generation.
The authors note that further studies are required to clarify whether EBV plays a direct pathogenic role in RA or serves as an amplifier of existing autoimmune processes.
Reference
Kitamura N et al. Relationship between anti-Epstein-Barr virus early antigen diffuse type and restricted type immunoglobulin G antibodies and disease activity and autoantibodies in rheumatoid arthritis: a retrospective observational study. BMC Rheumatol. 2025;DOI: 10.1186/s41927-025-00576-x.
