SAT0617 PRESENCE OF ANTI-BETA2-GLYCOPROTEIN-1 IGA ANTIBODIES MODERATES THE EFFECT OF INFLAMMATORY BURDEN ON CORONARY PLAQUE PROGRESSION IN RHEUMATOID ARTHRITIS
Authors: George Karpouzas, Sarah Ormseth, Elizabeth Hernandez, Matthew Budoff
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Beta2-glycoprotein-1 (b2GPI), an apolipoprotein abundant in human plasma, is readily expressed in human atherosclerotic plaque. High frequencies of anti-b2GPI-IgA antibodies have been previously reported in both Rheumatoid arthritis (RA) patients and controls; their presence has been independently predictive of cardiovascular events in general patients. <h3>Objectives</h3> We explored the role of a-b2GPI-IgA presence and their interaction with inflammatory load on occult coronary plaque progression in patients with RA. <h3>Methods</h3> One hundred-one participants with a baseline plaque evaluation with coronary computed tomography angiography (CCTA) underwent follow-up assessment within 83±3.6 months. Coronary artery calcium (CAC) was quantified by the Agatston method. Subclasses (IgG, IgM, and IgA) of a-b2GPI Ab, anticardiolipin-Ab (ACL) and lupus anticoagulant (LA) were assessed on the day of baseline CCTA and reconfirmed 12 weeks later, if positive. Serum interleukin-6 (IL-6) was measured at baseline scan, while CRP was assessed on every clinic visit from baseline through follow-up scan. Multivariate linear regression models evaluated predictors of CAC progression; predictors entered as continuous variables included baseline CAC, age, waist-to-height ratio (obesity index), cumulative prednisone dose, years exposure to bDMARDs, statins and baseline IL-6 or time-averaged CRP. Gender, diabetes, hypertension, dyslipidemia, and a-b2GPI-IgA positivity were entered as dichotomous independent variables. Specific interactions between a-b2GPI-IgA presence (predictor) and time-averaged CRP or baseline IL-6 (moderator) where explored; the conditional effects of the predictor at values of the moderator and significance regions were defined with the Johnson-Neyman test. <h3>Results</h3> A-b2GPI-IgA antibodies were highly prevalent (34.7%) in contrast to other antiphospholipid-Ab subclasses (&lt;4%). A-b2GPI-IgA presence predicted incident CAC [OR=3.69 (1.02-13.32), p=0.046] as well as greater CAC change from baseline, after adjustments for age, baseline CAC score and significant covariates [mean change (95%CI) = 93.2 (69.8-116.6) vs. 56.0 (39.0-73.0) units, p=0.012]. A significant interaction between a-b2GPI-IgA positivity and time-averaged CRP as well as baseline IL-6 on CAC progression was observed [beta=0.19, p=0.048 for time-averaged CRP and beta=0.26, p=0.029 for IL-6 respectively]; higher baseline IL-6 and time-averaged CRP associated with significant CAC progression exclusively in a-b2GPI-IgA positive patients but not in those without such Ab. Baseline IL-6&gt; 4.66pg/ml and time-averaged CRP&gt; 0.76mg/dl both associated with significantly higher CAC progression in a-b2GPI-IgA positive patients but not in negative ones (figure 1). <h3>Conclusion</h3> A-b2GPI-IgA antibodies independently contributed to occult coronary plaque progression in RA and specifically moderated the effect of inflammation on progression of atherosclerotic burden. Tight control of inflammation may be particularly important in Ab positive patients in order to prevent coronary plaque progression; additionally, a-b2GPI-IgA presence may serve as a predictive biomarker for atherosclerosis progression, especially in the context of higher inflammatory state. <h3>Disclosure of Interests</h3> George Karpouzas Grant/research support from: Pfizer, Consultant for: Sanofi-Genzyme-Regeneron, Janssen, Roche-Genentech, Pfizer, Speakers bureau: BMS, Sanofi-Genzyme-Regeneron, Janssen, Roche-Genentech, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared