title: Anti-type II collagen antibodies are associated with early radiographic destruction in rheumatoid arthritis.
abstract: BACKGROUND
  We have previously reported that high levels of antibodies specific for native human type II collagen (anti-CII) at the time of RA diagnosis were associated with concurrent but not later signs of inflammation. This was associated with CII/anti-CII immune complex (IC)-induced production of pro-inflammatory cytokines in vitro. In contrast, anti-cyclic citrullinated peptide antibodies (anti-CCP) were associated both with late inflammation and late radiological destruction in the same RA cohort. We therefore hypothesized that anti-CII are also associated with early erosions.
  
  
  METHODS
  Two-hundred-and-fifty-six patients from an early RA cohort were included. Baseline levels of anti-CII, anti-CCP and anti-mutated citrullinated vimentin were analyzed with ELISA, and rheumatoid factor levels were determined by nephelometry. Radiographs of hands and feet at baseline, after one and after two years were quantified using the 32-joints Larsen erosion score.
  
  
  RESULTS
  Levels of anti-CII were bimodally distributed in the RA cohort, with a small (3.1%, 8/256) group of very high outliers with a median level 87 times higher than the median for the healthy control group. Using a cut-off discriminating the outlier group that was associated with anti-CII IC-induced production of proinflammatory cytokines in vitro, baseline anti-CII antibodies were significantly (p = 0.0486) associated with increased radiographic damage at the time of diagnosis. Anti-CII-positive patient had also significantly increased HAQ score (p = 0.0303), CRP (p = 0.0026) and ESR (p = 0.0396) at the time of diagnosis but not during follow-up. The median age among anti-CII-positive subjects was 12 years higher than among the anti-CII-negative patients.
  
  
  CONCLUSIONS
  In contrary to anti-CCP, anti-CII-positive patients with RA have increased joint destruction and HAQ score at baseline. Anti-CII thus characterizes an early inflammatory/destructive phenotype, in contrast to the late appearance of an inflammatory/destructive phenotype in anti-CCP positive RA patients. The anti-CII phenotype might account for part of the elderly acute onset RA phenotype with rather good prognosis.
authors.affiliation: Clinical Immunology, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory C5, Uppsala University, Uppsala, SE-75185, Sweden.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mullazehi
authors.forename: Marius C
authors.initials: MC
authors.lastname: Wick
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Ronald
authors.initials: R
authors.lastname: van Vollenhoven
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II