Maintenance of cytomegalovirus-specific CD4(pos )T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments

INTRODUCTION: Anti-tumor necrosis factor (TNF)-α biotherapies have considerably changed the treatment of rheumatoid arthritis (RA). However, serious infections are a major concern in patients with rheumatic diseases treated with anti-TNF-α. Little is known about viral, especially latent, infections in anti-TNF-α treatments. Infections by cytomegalovirus (CMV), a β-herpes virus, are frequent and induce a strong CD4(pos )T-cell immunity, which participates in the control of infection. We thus have chosen to analyze the CD4(pos )T-cell response to CMV antigens as a model of antiviral response in RA patients treated with anti-TNF-α. CD28 expression was evaluated. METHODS: We have measured the CD4(pos )response to CMV antigens in RA patients, before and after initiation of treatment with an anti-TNF-α agent. The intracellular production of interferon (IFN)-γ in total and CD28(neg )CD4(pos )T cells in response to CMV antigens (Ags) was evaluated with flow cytometry. The proliferation of total CD4(pos )T cells in the presence of CMV antigens was measured with (3)H-thymidine incorporation. RESULTS: Anti-TNF-α treatments impaired neither the anti-CD4(pos )anti-CMV IFN-γ response nor the proliferative response in patients. The percentage of CD28(neg )CD4(pos )cells remained constant. CONCLUSIONS: Our data suggest that the CD4(pos )T-cell response against CMV is not altered by anti-TNF-α treatments and that infection remains controlled in treated RA patients latently infected with CMV. Our observation brings new insight into the current knowledge of the risks of infection in patients treated with anti-TNF-α biotherapies.