title: Anti-nuclear antibodies, anti-DNA and C4 complement evolution in rheumatoid arthritis and ankylosing spondylitis treated with TNF-alpha blockers.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, University Hospital Pellegrin, Bordeaux Cedex, France. camille.gracia@chu-bordeaux.fr
authors.forename: C
authors.initials: C
authors.lastname: Gonnet-Gracia
authors.forename: T
authors.initials: T
authors.lastname: Barnetche
authors.forename: C
authors.initials: C
authors.lastname: Richez
authors.forename: P
authors.initials: P
authors.lastname: Blanco
authors.forename: J
authors.initials: J
authors.lastname: Dehais
authors.forename: T
authors.initials: T
authors.lastname: Schaeverbeke
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D016516:CD4-CD8 Ratio; D003181:Complement C4 / Q000378:metabolism*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D003181:Complement C4; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept