title: Antibodies binding to citrullinated telopeptides of type I and type II collagens and to mutated citrullinated vimentin synergistically predict the development of seropositive rheumatoid arthritis.
abstract: OBJECTIVE
  To assess whether antibodies binding to citrullinated carboxy-terminal telopeptides of type I and type II collagens (TELO-I and TELO-II, respectively), mutated citrullinated vimentin (MCV) and cyclic citrullinated peptides (CCP) predict the development of rheumatoid arthritis (RA).
  
  
  METHODS
  A case-control study was nested within a Finnish cohort of 36 000 adults who had neither arthritis nor a history of arthritis at baseline examination in 1966-1972. Among them, 151 subjects developed seropositive (ie, positive for rheumatoid factor) RA, and 67 subjects developed seronegative RA by late 1989. One or two control subjects were chosen for every case. Preillness serum specimens were analysed for antibodies against synthetic TELO-I, TELO-II, MCV and CCP.
  
  
  RESULTS
  The mean levels of anti-TELO-I, anti-TELO-II, anti-CCP and anti-MCV antibodies were higher in subjects who later developed seropositive or seronegative RA than in controls. In subjects who later developed seronegative RA, anti-TELO-I and anti-TELO-II antibodies were statistically significantly higher compared with controls (p=0.005 and p=0.013). In the highest tertiles of anti-MCVs and anti-TELO-I levels, the OR for rheumatoid-factor-positive RA were 2.66 (95% CI 1.48 to 4.77) or 2.51 (CI 1.48 - 4.28), respectively. The subjects ranked into the highest tertiles of both anti-TELO-I and anti-MCV antibodies had a 4.56 OR (95% CI 1.82 to 11.46) of developing seropositive RA compared with those in the lowest tertiles of these antibodies. For the co-occurrence for high anti-TELO-II and anti-MCV antibodies, the corresponding OR was 3.62 (95% CI 1.37 to 9.54).
  
  
  CONCLUSIONS
  Antibodies to TELO-I or TELO-II and MCV exert a synergistic effect on the risk of developing seropositive RA.
authors.affiliation: Institute of Diagnostics, Department of Clinical Chemistry, University of Oulu, PO Box 5000, FI-90014 Oulu, Finland.
authors.forename: Marja-Kaisa
authors.initials: MK
authors.lastname: Koivula
authors.forename: Markku
authors.initials: M
authors.lastname: Heliövaara
authors.forename: Harri
authors.initials: H
authors.lastname: Rissanen
authors.forename: Timo
authors.initials: T
authors.lastname: Palosuo
authors.forename: Paul
authors.initials: P
authors.lastname: Knekt
authors.forename: Heikki
authors.initials: H
authors.lastname: Immonen
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002956:Citrulline / Q000276:immunology; D024042:Collagen Type I / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D014746:Vimentin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D014746:Vimentin; D002956:Citrulline