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


METHODS
We 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.


RESULTS
Anti-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.


CONCLUSIONS
Our 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.
Davignon
Jean-Luc
JL
University Paul Sabatier Toulouse III, France. ean-luc.davignon@inserm.fr
Boyer
Jean-Frédéric
JF
Jamard
Bénédicte
B
Nigon
Delphine
D
Constantin
Arnaud
A
Cantagrel
Alain
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000956:Antigens, Viral; D018106:CD28 Antigens; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma