Abstract 331: 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. Anti-ApoA-I IgG antibodies targeting delipidated ApoA-I have previously been characterized as a biomarker of cardiovascular disease progression, but only moderate associations have been reported. We hypothesize that antibodies bound to ApoA-I as an immune complex are a critical and unexplored component of the antibody response to ApoA-I, which will better predict disease outcomes. To test this hypothesis we developed an ELISA assay to quantify IgG bound to ApoA-I as a soluble immune complex (IC) in sera samples. This ELISA assay was used to screen plasma from 359 patients with coronary artery disease (CAD). Analysis of outcomes in these patients shows that patients in the lowest tertile for ApoA-I/IgG IC values have an increased risk for death and non-fatal myocardial infarction as compared to patients in the highest tertile with an hazard ratio of 1.89 (95% CI: 1.02 - 3.52; p = 0.04) after adjustment for 6 common cardiovascular risk factors. Pearson correlation analysis between ApoA-I/IgG ICs in the 359 patients with CAD found no relationship between ApoA-I/IgG ICs and 26 common clinical measures. In a second cohort of 104 blood donors, ApoA-I/IgG IC levels in sera were compared to the concentration of the individual components. No significant relationship between ApoA-I/IgG ICs and total ApoA-I concentration (113 ± 44 mg/dL, r 2 = 0.0075) was observed, while a weak correlation was observed between ApoA-I/IgG IC level and total IgG concentration (12 ± 4 mg/mL r 2 = 0.089). The antibody subclass composition of ApoA-I/IgG IC were then characterized and found to be enriched in IgG4, the anti-inflammatory subclass as compared to the subclass percentage in total serum (36% and 7%, p = 0.0381). The enrichment in the anti-inflammatory IgG4 provides a potential mechanisms of the protective effect of ApoA-I/IgG ICs in patients. The identification and further characterization of ApoA-I/IgG ICs has the potential to guide clinical diagnosis and intervention strategies in patients with atherosclerotic cardiovascular disease.