Association of anticytomegalovirus seropositivity with more severe joint destruction and more frequent joint surgery in rheumatoid arthritis

Abstract Objective Expansion of autoreactive CD4+CD28 null T cells is associated with extraarticular disease manifestations, including rheumatoid vasculitis, and it has recently been demonstrated that expansion of these T cells is associated with anticytomegalovirus (anti‐CMV) seropositivity. This study was undertaken to investigate a possible link between latent CMV infection and rheumatoid arthritis (RA). Methods In a retrospective analysis, anti‐CMV antibodies and clinical, serologic, and radiologic parameters of joint destruction were examined in 202 RA patients and 272 healthy controls. In addition, frequencies of CD4+CD28 null T cells; concentrations of the cytokines monocyte chemotactic protein 1 (MCP‐1), interferon‐α (IFNα), and IFN‐inducible protein 10; and anti‐CMV–specific T cell responses were analyzed in RA patients. Results Overall, no significant difference in the frequency of anti‐CMV seropositivity between RA patients and healthy controls was observed. Among individuals older than age 55 years, however, anti‐CMV IgG antibodies were significantly more frequent in RA patients than controls (65.3% and 54.7%, respectively; P = 0.05). Anti‐CMV seropositivity in RA patients was associated with an increased frequency of CD4+CD28 null T cells and increased serum concentrations of MCP‐1. The frequency of anti‐CMV–specific CD4+ T cells producing IFNγ was increased in RA patients compared to controls. Most importantly, anti‐CMV–seropositive RA patients showed radiographic evidence of more advanced joint destruction and had increased frequencies of joint‐related surgical procedures, indicating more severe joint disease. Conclusion Our findings indicate that latent CMV infection aggravates the clinical course of RA and is associated with increased frequencies of CD4+CD28 null T cells and of CMV‐specific IFNγ‐secreting CD4+ T cells.