title: Neo-Epitopes--Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis.
abstract: OBJECTIVE
  Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis.
  
  
  METHODS
  Ninety-two early arthritis patients (arthritis duration<1 year, DMARD naïve) were enrolled. Patients either fulfilled the ACR/EULAR2010 criteria for RA (n = 60) or had unclassified arthritis (UA) (n = 32). Patients fulfilling the RA criteria after 2 years follow-up were classified into non-erosive (n = 25), or erosive disease (n = 13). Concentrations of the biomarkers: C1M, C2M, C3M, VICM and CRPM were measured in baseline serum.
  
  
  RESULTS
  C1M, C3M and CRPM were able to discriminate between the UA and RA baseline diagnosis in 92 patients with an AUROC of 0.64 (95%CI 0.517 to 0.762), 0.73 (95%CI 0.622 to 0.838) and 0.68 (95%CI 0.570 to 0.795). C2M showed a potential for discrimination between non-erosive and erosive disease in 38 patients with an AUROC of 0.75 (95%CI 0.597 to 0.910). All of the applied biomarkers correlated with one or more of the disease activity parameters: DAS28, ESR, CRP, SJC66, TJC68 and/or HAQ.
  
  
  CONCLUSIONS
  This is the first study evaluating the applied biomarkers at this early stage of arthritis. C1M, C3M, CRPM might be the best diagnostic marker, whereas high levels of C2M indicated progression of disease at follow-up in early RA patients.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Karen I
authors.initials: KI
authors.lastname: Maijer
authors.affiliation: Nordic Bioscience, Herlev, Denmark.|University of Southern Denmark, Odense, Denmark.
authors.forename: Natasja Stæhr
authors.initials: NS
authors.lastname: Gudmann
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Morten Asser
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Daniëlle M
authors.initials: DM
authors.lastname: Gerlag
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Paul Peter
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Nordic Bioscience, Herlev, Denmark.
authors.forename: Anne Christine
authors.initials: AC
authors.lastname: Bay-Jensen
mesh_terms: D000328:Adult; D001168:Arthritis / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002356:Cartilage / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood; D024061:Collagen Type III / Q000097:blood; D003238:Connective Tissue / Q000378:metabolism*; D018450:Disease Progression; D000939:Epitopes / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D014746:Vimentin / Q000097:blood
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D000939:Epitopes; D014746:Vimentin; D002097:C-Reactive Protein; D020782:Matrix Metalloproteinases