Key Autoantibody and Inflammatory Factors in the Initiation, Propagation, and Transition to Clinically Apparent Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with the hallmark clinical finding of inflammatory arthritis (IA). RA affects ~1 of the population leading to substantial morbidity, increased mortality and high financial costs. The current paradigm for management of RA is to identify a patient with disease and treated once clinical signs of disease (e.g. joint pain and swelling) have been identified. However, there is now known to be a Pre-RA period of RA during which circulating biomarkers including autoantibodies are present on average 3-5 years prior to the first appearance of clinically-apparent IA. Importantly, elevations of serum autoantibodies (e.g. antibodies to citrullinated protein antibodies [ACPA] and rheumatoid factor [RF]) can be used to accurately predict future RA in individuals without current IA. Indeed, the predictive ability of these autoantibodies has underpinned the development of several clinical prevention trials for RA. However, there are still substantial limits in prediction models for future RA; furthermore, specific biologic pathways that could be targeted in Pre-RA for prevention need additional exploration. As such, the primary objective for this project is to build on our initial findings from a prior CDMRP project and utilize a unique sample set of individuals from pre- and post-RA diagnosis obtained from the Department of Defense Serum Repository (DoDSR) to expand our knowledge about the development of RA and in particular improve prediction of future RA as well as identify potential pathways/targets for prevention by utilizing state-of-the-art biomarker testing.