title: Autoantibodies to posttranslationally modified type II collagen as potential biomarkers for rheumatoid arthritis.
abstract: OBJECTIVE
  Type II collagen (CII) posttranslationally modified by reactive oxygen species (ROS-CII) that are present in the inflamed joint is an autoantigen in rheumatoid arthritis (RA). The aim of this study was to investigate the potential use of anti-ROS-CII autoantibodies as a biomarker of RA.
  
  
  METHODS
  CII was exposed to oxidants that are present in the rheumatoid joint. Autoreactivity to ROS-CII was assessed by enzyme-linked immunosorbent assays in synovial fluid (SF) and serum samples obtained from patients during various phases of RA. This group included disease-modifying antirheumatic drug (DMARD)-naive patients with early RA (n = 85 serum samples) and patients with established RA (n = 80 serum and 50 SF samples), who were categorized as either DMARD responders or DMARD nonresponders. Control subjects included anti-citrullinated protein antibody (ACPA)-positive patients with arthralgia (n = 58 serum samples), patients with osteoarthritis (OA; n = 49 serum and 52 SF samples), and healthy individuals (n = 51 serum samples).
  
  
  RESULTS
  Reactivity to ROS-CII among DMARD-naive patients with early RA was significantly higher than that among patients with ACPA-positive arthralgia, patients with OA, and healthy control subjects (P < 0.0001), with 92.9% of serum samples from the patients with early RA binding to anti-ROS-II. There was no significant difference in anti-ROS-CII reactivity between ACPA-positive and ACPA-negative patients with RA, with 93.8% and 91.6% of serum samples, respectively, binding to ROS-CII. The sensitivity and specificity of binding to ROS-CII in patients with early RA were 92% and 98%, respectively. Among patients with established RA, serum reactivity in DMARD nonresponders was significantly higher than that in DMARD responders (P < 0.01); 58.3% of serum samples from nonresponders and 7.6% of serum samples from responders bound to HOCl-ROS, while the respective values for SF were 70% and 60%. In patients with longstanding RA, autoreactivity to ROS-CII changed longitudinally.
  
  
  CONCLUSIONS
  Autoantibodies to ROS-CII have the potential to become diagnostic biomarkers of RA.
authors.affiliation: Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Rocky
authors.initials: R
authors.lastname: Strollo
authors.forename: Frederique
authors.initials: F
authors.lastname: Ponchel
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
authors.forename: Michele
authors.initials: M
authors.lastname: Bombardieri
authors.forename: Claire Y
authors.initials: CY
authors.lastname: Wenham
authors.forename: Rebecca
authors.initials: R
authors.lastname: Landy
authors.forename: David
authors.initials: D
authors.lastname: Perret
authors.forename: Fiona
authors.initials: F
authors.lastname: Watt
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Corrigall
authors.forename: Paul G
authors.initials: PG
authors.lastname: Winyard
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Panayi
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Ahuva
authors.initials: A
authors.lastname: Nissim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000276:immunology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers; D016022:Case-Control Studies; D024043:Collagen Type II / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000276:immunology; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000276:immunology*; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D024043:Collagen Type II; D010456:Peptides, Cyclic; D010750:Phosphoproteins; C097756:cyclic AMP-dependent phosphoprotein (rod outer segment); C487763:cyclic citrullinated peptide