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

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.