title: Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis.
abstract: OBJECTIVE
  Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.
  
  
  METHODS
  A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years.
  
  
  RESULTS
  Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals.
  
  
  CONCLUSIONS
  Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.
authors.affiliation: Department of Rheumatology, Odense University Hospital, Odense, Denmark. a.friesgaard@gmail.com
authors.forename: Anne F
authors.initials: AF
authors.lastname: Christensen
authors.forename: Hanne
authors.initials: H
authors.lastname: Lindegaard
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.forename: Merete L
authors.initials: ML
authors.lastname: Hetland
authors.forename: Bo
authors.initials: B
authors.lastname: Ejbjerg
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Tine
authors.initials: T
authors.lastname: Lottenburger
authors.forename: Torkell
authors.initials: T
authors.lastname: Ellingsen
authors.forename: Lis S
authors.initials: LS
authors.lastname: Andersen
authors.forename: Ib
authors.initials: I
authors.lastname: Hansen
authors.forename: Henrik
authors.initials: H
authors.lastname: Skjødt
authors.forename: Jens K
authors.initials: JK
authors.lastname: Pedersen
authors.forename: Ulrik B
authors.initials: UB
authors.lastname: Lauridsen
authors.forename: Anders
authors.initials: A
authors.lastname: Svendsen
authors.forename: Ulrik
authors.initials: U
authors.lastname: Tarp
authors.forename: Jan
authors.initials: J
authors.lastname: Pødenphant
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D001323:Autoantibodies / Q000276:immunology*; D064236:Cartilage Oligomeric Matrix Protein; D002986:Clinical Trials as Topic; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D010147:Pain Measurement; D010456:Peptides, Cyclic / Q000276:immunology*; D011795:Surveys and Questionnaires; D013585:Synovitis / Q000276:immunology / Q000473:pathology*
chemical_list: D001323:Autoantibodies; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D010456:Peptides, Cyclic; C577553:TSP5 protein, human; C487763:cyclic citrullinated peptide