Autoantibodies to Posttranslationally Modified Type II Collagen as Potential Biomarkers for Rheumatoid Arthritis

Abstract

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