OP0118 DISCRETE PATTERNS OF CITRULLINATED PEPTIDE AUTOANTIBODY REACTIVITIES EMERGE DURING PROGRESSION FROM PRE-DISEASE STATE TO DIAGNOSIS OF RHEUMATOID ARTHRITIS

Abstract

Background Rheumatoid Arthritis (RA) patients with established disease can have autoantibodies reactive to a broad array of citrullinated antigens. Autoantibodies reactive against several citrullinated proteins can develop 10-15 years before the clinical onset of disease. Objectives We aimed to identify common patterns of citrullinated peptide reactivities that emerge among subjects during progression from a pre-disease state through diagnosis of RA. Methods 500 subjects with RA (based on ICD9-CM code) were identified from the Defense Medical Surveillance System. For each subject, up to four serum samples were obtained from the Department of Defense (DoD) serum repository: 1 from earliest time point before diagnosis (9.2 ± 2.0 years before, mean ± SD); one proximal to (immediately prior to or after) disease diagnosis (127 ± 125 days before diagnosis); plus 2 intermediate time points. A discovery subset of serum samples from 88 RA subjects confirmed to be positive for anti-citrullinated protein antibodies (ACPA) at the diagnosis-proximal time point (>5 U/mL for cyclic citrullinated peptide (CCP)-II test) was assessed for IgG antibodies to 36 antigens (24 citrullinated-peptide antigens among 14 proteins and 12 non-citrullinated antigens among 9 proteins) using a custom Luminex-based assay. Subjects testing above the upper limit of detection for the CCP-II test (300 U/mL) were considered ACPA-high (n=28), with the remainder considered moderate (n=60). Results For the group of ACPA-high subjects at the diagnosis-proximal time point, average IgG autoantibody binding to 9 citrullinated peptide antigens (from 7 proteins: clusterin, enolase, fibrinogen A, fibrinogen B, fibronectin, filaggrin, vimentin) showed significant increases from the earliest through diagnosis-proximal time points at the population level (FDR Conclusion Novel patterns of citrullinated peptide autoantibody reactivities that begin to emerge on average about 6 years before diagnosis of RA have been identified in samples from the US DoD serum repository. Evaluation of specific anti-citrullinated peptide autoantibodies could potentially provide sensitive, patient-tailored biomarkers to monitor disease trajectories as at-risk individuals progress to clinically-defined RA. Disclosure of Interests:  Matthew J Loza Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Sunil Nagpal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Renee Laird: None declared, Suzanne Cole Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Frederic Baribaud Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Ian Anderson Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Navin Rao Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Mark Riddle: None declared, Chad Porter: None declared