THE IFN TYPE I GENE EXPRESSION IN A CARDIOVASCULAR DISEASE CONTINUUM OF RHEUMATOID ARTHRITIS

Introduction Rheumatoid Arthritis (RA) patients have a prominent increase in cardiovascular (CV) comorbidity not fully explained by traditional risk factors. 1 Interferons type 1 (IFN-1) have been associated with premature CV disease (CVD) in SLE 2 and are implicated in several aspects of atherosclerosis and acute coronary syndromes. 3 In RA a subpopulation of patients also display an IFN-1 signature in the blood, 4 which is associated with response to biologics. The IFN- 1 signature association with CVD in RA remains unclear. Objectives To analyse expression of interferon type 1 response genes (ISGs) along a CVD continuum in patients with RA using a well phenotyped cohort of RA patients whereby cardiovascular changes were assessed by Cardiac Magnetic Resonance Imaging (CMR). Methods PBMCs samples from 60 RA patients (mean (90% CI)) age 62.4 (60.2, 64.6)y.o, sex F/M 42/18, disease duration 153.3 (121.3, 185.2) mths and n=18 healthy controls (HC); age 42 (37.8,46.0) y, F/M 12/6 were obtained. RA patients were stratified based on CMR into: no CVD (RA CMRneg n=13) and abnormal CMR (RA CMRpos n=26), and RA with clinical CVD (no CMR, defined as history of cerebrovascular disease or ischaemic heart disease) (RA CVD n=21). qPCR of ISGs was performed using TaqMan Gene Expression Assays on Biomark (Fluidigm). Factor scores were created using the set of 51 genes measured in 78 subjects. Results All routinely used biomarkers were associated with RA diagnosis (ACPA, RF, TJC, SJC, CRP, DAS28). Total cholesterol and LDL levels were higher in RA than in HC group (p=0.051 and p=0.015). Three IFN-1 scores were present in the dataset (IFN Score 1, 2 and 3) and were composed of 19, 21 and 7 genes respectively. IFN-1 score 2 showed significant differences between HC and RA CMRpos groups (mean difference and 90% CI: 0.52 (0.09, 0.96)) and HC and RA CVD (0.57 (0.10, 1.03)) as well as all RA patients with CVD (CMRpos and RA CVD) ((0.54 (0.16, 0.93); p Conclusions An IFN-1 score 2 emerged as a possible factor characterising progression along a CVD continuum in RA patients, from no CVD to subclinical and clinical CVD; also distinguishing between HC and RA with subclinical and clinical CVD. These results warrant further evaluation in a larger cohort to confirm the findings. References . Kaplan MJ. Curr. Opin. Rheumatol2006;18(3):289–297. . Somers EC, et al. PloS One2012;7(5):e37000. . de Winther MPJ. Arterioscler. Thromb. Vasc. Biol2016;36(2):217–218. . van der Pouw Kraan TC, et al. Ann. Rheum. Dis2007;66(8):1008–1014. Disclosure of interest None declared