Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies.
BACKGROUND
There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy.


METHODS
Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNgamma-producing T cells in response to EBV latent-cycle and lytic-cycle peptides.


RESULTS
The EBV load and the number of IFNgamma-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution.


CONCLUSIONS
These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded.
Miceli-Richard
Corinne
C
Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin Bicêtre, France. corinne.miceli@bct.aphp.fr
Gestermann
Nicolas
N
Amiel
Corinne
C
Sellam
Jérémie
J
Ittah
Marc
M
Pavy
Stephan
S
Urrutia
Alejandra
A
Girauld
Isabelle
I
Carcelain
Guislaine
G
Venet
Alain
A
Mariette
Xavier
X
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology / Q000821:virology; D003430:Cross-Sectional Studies; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D025242:Spondylarthropathies / Q000097:blood* / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D019562:Viral Load / Q000379:methods
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate