Autoantibodies to posttranslationally modified type II collagen as potential biomarkers for rheumatoid arthritis

Rocky Strollo, Frederique Ponchel, Vivianne Malmström, Paola Rizzo, Michele Bombardieri, Claire Y Wenham, Rebecca Landy, David Perret, Fiona Watt, Valerie M Corrigall, Paul G Winyard, Paolo Pozzilli, Philip G Conaghan, Gabriel S Panayi, Lars Klareskog, Paul Emery, Ahuva Nissim

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

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.

CONCLUSION: Autoantibodies to ROS-CII have the potential to become diagnostic biomarkers of RA.

Original languageEnglish
Pages (from-to)1702-1712
Number of pages11
JournalArthritis & Rheumatism
Volume65
Issue number7
DOIs
Publication statusPublished - 1 Jul 2013

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents
  • Arthritis, Rheumatoid
  • Autoantibodies
  • Biological Markers
  • Case-Control Studies
  • Collagen Type II
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis
  • Peptides, Cyclic
  • Phosphoproteins
  • Protein Processing, Post-Translational
  • Severity of Illness Index
  • Synovial Fluid
  • Young Adult

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