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Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies

Corinne Miceli-Richard12, Nicolas Gestermann2, Corinne Amiel3, Jérémie Sellam12, Marc Ittah2, Stephan Pavy1, Alejandra Urrutia2, Isabelle Girauld2, Guislaine Carcelain4, Alain Venet2 and Xavier Mariette12*

Author Affiliations

1 Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France

2 Institut Pour la Santé et la Recherche Médicale (INSERM) U 802, Université Paris-Sud 11, 64 rue Gabriel Péri, 94275 Le Kremlin Bicêtre, France

3 Virologie, Hôpital Tenon, AP-HP, 4 rue de la Chine, 75020 Paris, France

4 INSERM U543, Hôpital La Pitié Salpétrière, AP-HP, 47 Boulevard de l'Hôpital, 75013 Paris, France

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Arthritis Research & Therapy 2009, 11:R77  doi:10.1186/ar2708

Published: 26 May 2009



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.


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 IFNγ-producing T cells in response to EBV latent-cycle and lytic-cycle peptides.


The EBV load and the number of IFNγ-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.


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.