title: Induction of autoantibodies in refractory rheumatoid arthritis treated by infliximab.
abstract: OBJECTIVE
  To investigate autoantibody induction in rheumatoid arthritis (RA) patients treated with infliximab.
  
  
  METHODS
  We included 59 refractory RA patients treated with infliximab in combination with low-dose prednisone and methotrexate or leflunomide. We tested the sera of the patients for antinuclear antibodies (ANA), rheumatoid factor (RF), anti double-stranded DNA antibodies (anti dsDNA), anti-histone and anti-extractable nuclear antigen antibodies (aENA) at baseline and before infusion at weeks 6 and 30. Infliximab, initiated at a dose of 3 mg/kg, was increased to 5 mg/kg if insufficient improvement was observed after three infusions.
  
  
  RESULTS
  At week 6, only the frequency of anti-histone IgM antibody-positive patients had significantly increased (19 vs 42%, p = 0.009). At week 30, the frequency of patients with ANA had increased from 29% to 69% (p < 0.001), that of patients with anti-dsDNA antibodies had increased from 0% to 3% for IgG (NS) and from 0% to 32% for IgM (p < 0.001); the frequency of antihistone IgG detection had increased from 22% to 32% (p = 0.04) and that of IgM detection, from 18% to 79% (p < 0.001). No lupus-like syndrome was observed. RF decreased significantly (87 IU to 52.5 IU, from baseline to week 30; p < 0.001). No significant difference was observed between the 16 non-responders and the responders, in terms of autoantibody status at baseline and changes with infliximab therapy.
  
  
  CONCLUSIONS
  Infliximab therapy lead to the selective and delayed induction of autoantibodies. This induction was not associated with clinical symptoms until week 30 and did not differ between responders and non-responders.
authors.affiliation: Rheumatology A Department, Paris V University, Cochin Hospital, AP-HP Paris, France. yannick.allanore@cch.ap-hop-paris.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Allanore
authors.forename: J
authors.initials: J
authors.lastname: Sellam
authors.forename: F
authors.initials: F
authors.lastname: Batteux
authors.forename: C
authors.initials: C
authors.lastname: Job Deslandre
authors.forename: B
authors.initials: B
authors.lastname: Weill
authors.forename: A
authors.initials: A
authors.lastname: Kahan
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D000069285:Infliximab; D007555:Isoxazoles / Q000008:administration & dosage; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D011239:Prednisolone; D000069285:Infliximab; D000077339:Leflunomide; D008727:Methotrexate