Induction of autoantibodies in refractory rheumatoid arthritis treated by infliximab

Objectives. 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 anti-histone 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. Conclusion. 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.