Maintenance of cytomegalovirus-specific CD4pos T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments

Abstract

IntroductionAnti-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 CD4pos T-cell immunity, which participates in the control of infection. We thus have chosen to analyze the CD4pos T-cell response to CMV antigens as a model of antiviral response in RA patients treated with anti-TNF-α. CD28 expression was evaluated.MethodsWe have measured the CD4pos 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 CD28neg CD4pos T cells in response to CMV antigens (Ags) was evaluated with flow cytometry. The proliferation of total CD4pos T cells in the presence of CMV antigens was measured with 3H-thymidine incorporation.ResultsAnti-TNF-α treatments impaired neither the anti-CD4pos anti-CMV IFN-γ response nor the proliferative response in patients. The percentage of CD28neg CD4pos cells remained constant.ConclusionsOur data suggest that the CD4pos 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.

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

“…A proliferative response of CD4+ T cells toward CMV antigens as well as CMV‐specific IFNγ production has previously been shown to be present in RA (33), but, unlike in the present study, it was not compared to that in healthy controls. In healthy individuals, some studies have described higher frequencies of IFNγ‐secreting CD4+ T cells (24, 34), but the findings of other studies were more compatible with our results (35, 36).…”

Incidence of human cytomegalovirus infection and T-cell response in patients with psoriasis before and during antitumour necrosis factor-α therapy

“…In previous studies, anti‐TNF‐α treatment did not reduce interferon‐γ production or proliferation by HCMV‐specific T cells in patients with moderate‐to‐severe psoriasis or rheumatoid arthritis . Furthermore, we observed that anti‐TNF‐α drugs did not alter the polyfunctionality (ability of T‐cell subsets to produce more than one cytokine) of HCMV‐specific T cells (data not shown).…”

Systematic review: macrophage activation syndrome in inflammatory bowel disease

“…78 Concerning CMV, T-cell response to CMV was investigated in 25 patients on anti-TNF therapy, showing that the interferon-c response of CD4 + ve cells and the proliferative response were maintained upon CMV antigen stimulation. 79 Indeed, in most of the retrieved cases, and other reports on CMV infections 80 , patients were on concomitant thiopurine treatment. EBV is a virus with the potential of inducing malignant lymphomas, and many studies deal with this topic.…”

“…However, the overall risk of reactivation of latent herpes viruses in patients on biologics appears to be low; at least after 3 months of therapy in IBD and after 6 weeks in rheumatoid arthritis . Concerning CMV, T‐cell response to CMV was investigated in 25 patients on anti‐TNF therapy, showing that the interferon‐γ response of CD4 + ve cells and the proliferative response were maintained upon CMV antigen stimulation . Indeed, in most of the retrieved cases, and other reports on CMV infections, patients were on concomitant thiopurine treatment.…”