Anti-nuclear antibodies, anti-DNA and C4 complement evolution in rheumatoid arthritis and ankylosing spondylitis treated with TNF-alpha blockers

Clin Exp Rheumatol. May-Jun 2008;26(3):401-7.


Objective: To investigate autoantibody induction in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in a cohort of French patients treated with TNF-alpha blockers.

Methods: We tested the serum of patients for antinuclear antibodies (ANA), anti-DNA antibodies and C4 complement at baseline, and for each infusion for infliximab, and at month 3, 6 and 12 for etanercept. We looked for all signs suggesting a drug-induced lupus. We tried to correlate ANA and anti-DNA development with various clinical data, especially the response to treatment.

Results: 229 patients were included in the study. 159 were treated with infliximab (98 RA and 61 AS) and 125 with etanercept (116 RA and 9 AS). In the infliximab group, 43.6% of RA patients and 27.1% of AS had significant levels of ANA at baseline. This proportion increased during the follow up to 73% in RA patients and 52% in AS patients. The proportion of patients positive for anti-DNA antibodies increased from 0% to 9.5% in RA group, and from 0% to 2% in AS group. In the etanercept group, 58.5% of these patients had significant levels of ANA at baseline; this proportion raised to 63.3% in patients previously treated with infliximab, and fell to 20.6% in the patients who never received TNF-alpha blockers. No significant variation of ANA, anti-DNA and C4 levels was observed in the etanercept group. Only three patients developed clinical manifestations (chilblain lupus) possibly related to these auto-antibodies, two with infliximab and one with etanercept.

Conclusion: The ANA induction was only observed under infliximab therapy. Thus, ANA induction seems not to be a therapeutic class effect. This difference between infliximab and etanercept treatment may be the consequence of differential capacity of a monoclonal antibody and a soluble receptor in inducing apoptotic cell death of the cells expressing TNF on their membrane.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antinuclear / blood*
  • Antibodies, Monoclonal / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • CD4-CD8 Ratio
  • Complement C4 / metabolism*
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Complement C4
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Etanercept