Infliximab, but not etanercept, induces IgM anti-double-stranded DNA autoantibodies as main antinuclear reactivity: biologic and clinical implications in autoimmune arthritis

Arthritis Rheum. 2005 Jul;52(7):2192-201. doi: 10.1002/art.21190.


Objective: To analyze the clinical and biologic correlates of autoantibody induction during longer-term tumor necrosis factor alpha (TNFalpha) blockade with either the monoclonal antibody infliximab or the soluble receptor etanercept.

Methods: Thirty-four patients with spondylarthropathy (SpA) and 59 patients with rheumatoid arthritis (RA) were treated with infliximab for 2 years. Additionally, 20 patients with SpA were treated with etanercept for 1 year. Sera were blindly analyzed for antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA) antibodies, and antihistone, anti-nucleosome, and anticardiolipin antibodies (aCL). The anti-dsDNA antibodies were isotyped.

Results: High numbers of infliximab-treated patients with SpA or RA had newly induced ANAs (61.8% and 40.7%, respectively) and anti-dsDNA antibodies (70.6% and 49.2%, respectively) after 1 year, but no further increase between year 1 and year 2 was observed. In contrast, induction of ANAs and anti-dsDNA antibodies was observed only occasionally in the etanercept-treated patients with SpA (10% of patients each). Isotyping revealed almost exclusively IgM or IgM/IgA anti-dsDNA antibodies, which disappeared upon interruption of treatment. Neither infliximab nor etanercept induced other lupus-related reactivities such as anti-ENA antibodies, antihistone antibodies, or anti-nucleosome antibodies, and no clinically relevant lupus-like symptoms were observed. Similarly, infliximab but not etanercept selectively increased IgM but not IgG aCL titers.

Conclusion: The prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNFalpha blockers, is largely restricted to short-term IgM responses, and is not associated with other serologic or clinical signs of lupus. Similar findings with aCL suggest that modulation of humoral immunity may be a more general feature of infliximab treatment.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antinuclear / immunology*
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • DNA / immunology*
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Immunoglobulin M / blood
  • Infliximab
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Immunoglobulin G
  • Immunoglobulin M
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • DNA
  • Infliximab
  • Etanercept