title: Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy.
abstract: OBJECTIVE
  To investigate the effect of infliximab treatment on antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), antinucleosome, antihistone, and anti-extractable nuclear antigen (anti-ENA) antibodies in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.
  
  
  METHODS
  Sera from 62 RA and 35 SpA patients treated with infliximab were tested at baseline and week 30 (RA group) or week 34 (SpA group). ANAs were tested by indirect immunofluorescence (IIF) on HEp-2 cells. Anti-dsDNA antibodies were detected by IIF on Crithidia luciliae and by enzyme-linked immunosorbent assay (ELISA) and were further isotyped with gamma, mu, and alpha chain-specific conjugates at various time points. Antinucleosome antibodies were tested by ELISA. Antihistone and anti-ENA antibodies were detected by line immunoassay.
  
  
  RESULTS
  Initially, 32 of 62 RA patients and 6 of 35 SpA patients tested positive for ANAs. After infliximab treatment, these numbers shifted to 51 of 62 (P < 0.001) and 31 of 35 (P < 0.001), respectively. At baseline, none of the RA or SpA patients had anti-dsDNA antibodies. After infliximab treatment, 7 RA patients (P = 0.016) and 6 SpA patients (P = 0.031) became positive for anti-dsDNA antibodies. All 7 anti-dsDNA-positive RA patients had IgM and IgA anti-dsDNA antibodies. Three of the 6 anti-dsDNA-positive SpA patients had IgM and IgA anti-dsDNA antibodies, and 2 had IgM anti-dsDNA antibodies alone. In both diseases, the IgM anti-dsDNA antibodies appeared before the IgA anti-dsDNA antibodies. During the observation period, no IgG anti-dsDNA antibodies or lupus symptoms were observed. The development of antinucleosome, antihistone, or anti-ENA antibodies following infliximab treatment was observed in some patients, but the numbers were not statistically significant.
  
  
  CONCLUSIONS
  Infliximab treatment may induce ANAs, and especially IgM and IgA anti-dsDNA antibodies, in RA and SpA patients. However, no anti-dsDNA IgG antibodies or lupus symptoms were observed during the period of observation in this study, and the development of antinucleosome, antihistone, or anti-ENA antibodies was not statistically significant. These observations do not exclude potential induction of clinically significant lupus in the long term, and further followup is therefore mandatory.
authors.affiliation: Ghent University Hospital, Belgium. leenderycke@hotmail.com
authors.forename: Leen
authors.initials: L
authors.lastname: De Rycke
authors.forename: Elli
authors.initials: E
authors.lastname: Kruithof
authors.forename: Nancy
authors.initials: N
authors.lastname: Van Damme
authors.forename: Ilse E A
authors.initials: IE
authors.lastname: Hoffman
authors.forename: Nancy
authors.initials: N
authors.lastname: Van den Bossche
authors.forename: Filip
authors.initials: F
authors.lastname: Van den Bosch
authors.forename: Eric M
authors.initials: EM
authors.lastname: Veys
authors.forename: Filip
authors.initials: F
authors.lastname: De Keyser
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D004247:DNA / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D004247:DNA; D000069285:Infliximab; D008727:Methotrexate