Abstract 579: Anti-apolipoprotein A-I Antibody Profile Correlates With Cardiovascular Disease Outcomes

Apolipoprotein A-I (ApoA-I) is a target of IgG autoantibody induction in patients, but the role of these antibodies has not been fully elucidated. Previous research has characterized anti-ApoA-I IgG antibodies targeting delipidated ApoA-I as a biomarker of cardiovascular progression, but only a moderate association was observed. We hypothesize that free anti-ApoA-I IgG is a single component of the anti-ApoA-I response and characterization of anti-ApoA-I antibody profiles will be more predictive of adverse cardiovascular outcomes. Given the relative concentrations of ApoA-I and anti-ApoA-I antibodies, we examined sera samples from 375 patients with coronary artery disease (CAD) to quantify soluble ApoA-I/IgG immune complexes (ICs). We found a range of ApoA-I/IgG IC concentrations in patients, irrespective of free anti-ApoA-I antibodies. While free antibodies failed to predict outcomes in this CAD cohort, a median Cox regression analysis over 6 years of follow-up determined a hazard ratio of 1.5 (95% CI: 1.03-2.18, p = 0.03) for patients with below median ApoA-I/IgG ICs levels after adjusting for 11 traditional cardiovascular risk factors. In comparison, a cohort of healthy subjects exhibited significantly higher ApoA-I/IgG ICs. Pearson correlation analysis between ApoA-I/IgG ICs in the 375 patients with CAD and 25 patient characteristics found that only hypertension showed a significant association with ApoA-I/IgG ICs (r = -0.154, p = 0.003). In addition, no significant relationship between ApoA-I/IgG ICs and total ApoA-I concentration (r = -0.0601, p = 0.51) or total IgG concentration (r = 0.134, p = 0.137) was observed. Continued characterization of the molecular characteristics and immunologic sequelae associated with the immune complexes will help determine the functional implications of ApoA-I/IgG ICs in vivo . Current data using affinity column purification shows co-elution of ApoA-I and IgG in patients with elevated levels of ApoA-I/IgG ICs. Furthermore, ApoA-I/IgG ICs elute through size exclusion chromatography in the HDL fraction. The identification and characterization of ApoA-I/IgG ICs has the potential to guide clinical diagnosis and intervention strategies in patients with atherosclerotic cardiovascular disease.