title: Increased cartilage turnover and circulating autoantibodies in different subsets before the clinical onset of rheumatoid arthritis.
abstract: BACKGROUND
  Previous studies have indicated that autoantibodies may be detected years before the clinical onset of rheumatoid arthritis (RA). Cartilage biomarkers, such as cartilage oligomeric matrix protein (COMP), have not been studied previously in samples collected before the diagnosis of RA.
  
  
  METHODS
  Between 1991 and 1996, 30 447 subjects were included in the Malmö Diet Cancer Study (MDCS). People who developed RA after inclusion were identified by linking the MDCS database to different Swedish registers. One matched control for each validated case was selected from the MDCS. IgG antibodies against cyclic citrullinated peptide (anti-CCP) and mutated citrullinated vimentin (anti-MCV) and IgM rheumatoid factor (IgM RF) were determined by ELISA. Serum COMP was measured with a sandwich ELISA.
  
  
  RESULTS
  172 incident cases of RA (median time from inclusion to diagnosis 5 years; range 1-13) were identified. Pre-RA cases were significantly more likely than controls to be positive for anti-CCP (21.9% vs 0.6%), anti-MCV (29.6% vs 3.0%) and IgM RF (18.9% vs 2.4%) (all p<0.001). Overall, mean serum COMP levels did not differ between cases and controls. Among pre-RA cases included 1-3 years before diagnosis, raised COMP (>12 U/l) was seen in a greater proportion of anti-CCP-negative than anti-CCP-positive subjects (50% vs 15%; p=0.04).
  
  
  CONCLUSIONS
  Increased cartilage turnover, measured by COMP, and circulating RA-specific antibodies may be distinct processes in the preclinical phase of RA.
authors.affiliation: Correspondence to Dr Carl Turesson, Department of Rheumatology, Skåne University Hospital, Södra Förstadsgatan 101, S-205 02 Malmö, Sweden. carl.turesson@med.lu.se
authors.forename: Carl
authors.initials: C
authors.lastname: Turesson
authors.forename: Ulf
authors.initials: U
authors.lastname: Bergström
authors.forename: Lennart T H
authors.initials: LT
authors.lastname: Jacobsson
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Göran
authors.initials: G
authors.lastname: Berglund
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D042241:Early Diagnosis; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D064235:Matrilin Proteins; D008498:Medical Record Linkage; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007075:Immunoglobulin M; D064235:Matrilin Proteins; D010456:Peptides, Cyclic; C577553:TSP5 protein, human; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor