Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis-induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations: a two-year prospective study

Arthritis Res Ther. 2004;6(6):R535-43. doi: 10.1186/ar1440. Epub 2004 Sep 23.


Treatment of rheumatoid arthritis (RA) with infliximab (Remicade) has been associated with the induction of antinuclear autoantibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibodies. In the present study we investigated the humoral immune response induced by infliximab against organ-specific or non-organ-specific antigens not only in RA patients but also in patients with ankylosing spondylitis (AS) during a two-year followup. The association between the presence of autoantibodies and clinical manifestations was then examined. The occurrence of the various autoantibodies was analyzed in 24 RA and 15 AS patients all treated with infliximab and in 30 RA patients receiving methotrexate but not infliximab, using the appropriate methods of detection. Infliximab led to a significant induction of ANA and anti-dsDNA autoantibodies in 86.7% and 57% of RA patients and in 85% and 31% of AS patients, respectively. The incidence of antiphospholipid (aPL) autoantibodies was significantly higher in both RA patients (21%) and AS patients (27%) than in the control group. Most anti-dsDNA and aPL autoantibodies were of IgM isotype and were not associated with infusion side effects, lupus-like manifestations or infectious disease. No other autoantibodies were shown to be induced by the treatment. Our results confirmed the occurrence of ANA and anti-dsDNA autoantibodies and demonstrated that the induction of ANA, anti-dsDNA and aPL autoantibodies is related to infliximab treatment in both RA and AS, with no significant relationship to clinical manifestations.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Antinuclear / biosynthesis
  • Antibodies, Antinuclear / blood*
  • Antibodies, Antiphospholipid / biosynthesis
  • Antibodies, Antiphospholipid / blood*
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Autoantigens / immunology
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Autoimmunity / drug effects
  • DNA / immunology
  • Follow-Up Studies
  • Glycoproteins / immunology
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / immunology
  • Immunosuppressive Agents / therapeutic use
  • Infliximab
  • Methotrexate / therapeutic use
  • Prospective Studies
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • beta 2-Glycoprotein I


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Antinuclear
  • Antibodies, Antiphospholipid
  • Antibodies, Monoclonal
  • Autoantigens
  • Glycoproteins
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • beta 2-Glycoprotein I
  • DNA
  • Infliximab
  • Methotrexate