title: Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies.
abstract: 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.
authors.affiliation: Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin Bicêtre, France. corinne.miceli@bct.aphp.fr
authors.forename: Corinne
authors.initials: C
authors.lastname: Miceli-Richard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gestermann
authors.forename: Corinne
authors.initials: C
authors.lastname: Amiel
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
authors.forename: Marc
authors.initials: M
authors.lastname: Ittah
authors.forename: Stephan
authors.initials: S
authors.lastname: Pavy
authors.forename: Alejandra
authors.initials: A
authors.lastname: Urrutia
authors.forename: Isabelle
authors.initials: I
authors.lastname: Girauld
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Alain
authors.initials: A
authors.lastname: Venet
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: 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
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate