SAT0103 LONGITUDINAL PRE-DISEASE TO DISEASE SERUM SAMPLES IDENTIFY BIOMARKERS THAT ARE UPREGULATED PRIOR TO THE DIAGNOSIS OF RHEUMATOID ARTHRITIS

Abstract

Background Rheumatoid Arthritis (RA) patients have autoantibodies reactive against several citrullinated peptides that develop 10-15 years before the clinical onset of disease. However, there is a more limited understanding of serological biomarkers of disease progression, specifically those that are upregulated in patients 6-18 months before the clinical diagnosis of RA. Objectives Identification of biomarkers that could classify patients 6-18 months before the clinical diagnosis of RA. Methods We identified 500 subjects with RA, 500 with Reactive Arthritis (ReA) (based on ICD9-CM code) as well as 250 age, gender and time-matched healthy control subjects from the Defense Medical Surveillance System (DMSS). For each subject, up to four serum samples were obtained from the Department of Defense (DoD) serum repository, 3 pre-disease diagnosis points and one immediately prior to or around disease diagnosis. A discovery subset of these serum samples was assessed for soluble PD-1 (sPD-1), as well as 497 protein analytes measured by SomaLogic SOMAscan proteomic platform. Results Serum levels of sPD-1 increased over time from pre-diagnosis to RA but trended to decrease over time in ReA subjects and healthy controls. A composite score of 24 SOMAscan analytes associated with recently diagnosed RA increased in serum 6-8 months before RA diagnosis and, to a lesser extent, before ReA diagnosis. IFN-inducible chemokines CXCL9 (MIG), CXCL10 (IP-10), CXCL12 (I-TAC), and CXCL13 (BLC) increased over time preceding RA but not ReA diagnosis. Acute phase proteins (CRP, SAA, haptoglobin) and MMP-3 increased before diagnosis in serum samples from both RA and ReA patients. These protein analytes represent potential new biomarkers of early RA. Conclusion Samples from the US DoD serum repository have identified novel biomarkers (sPD-1 and IFN-inducible chemokines) of early RA that are elevated within 8 months of disease diagnosis. These protein analytes may afford the opportunity to develop novel biomarker(s) for diagnosis and disease progression to early RA. An understanding of the role of these proteins could provide increased insight into RA pathogenesis prior to disease diagnosis. Disclosure of Interests Sunil Nagpal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Matthew J Loza Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Suzanne Cole Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Brittney Scott Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Renee Laird: None declared, 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