From the Department of Pharmaceutical Sciences, University of Kentucky, Lexington (D.H., D.N., V.J.V.).
Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA (A.S.T., A.A.Q.).
Arterioscler Thromb Vasc Biol. 2019 Sep;39(9):1884-1892. doi: 10.1161/ATVBAHA.119.312964. Epub 2019 Jul 18.
The immune response is linked to the progression of atherosclerotic cardiovascular disease (CVD). Free autoantibodies targeting ApoA-I (apolipoprotein A-I) have been identified as a component of the inflammatory milieu in patients and have a moderate association with CVD progression. Based on the presence of these antibodies and the high concentration of circulating ApoA-I, we hypothesized that antibodies bound to ApoA-I as an immune complex would be predictive of incident adverse CVD outcomes. Approach and Results: The presence of ApoA-I/IgG immune complexes (ICs) in plasma was confirmed by ELISA in 3 subject cohorts. Characterization of the protein components of ApoAI/IgG ICs indicate that ICs are not correlated with total ApoA-I concentration and are enriched in the anti-inflammatory subclass, IgG4, relative to total plasma IgG (>30% versus 6%). In 359 patients with coronary artery disease (CAD), there were 71 incident adverse CVD events (death, myocardial infarction, and stroke) during a median 4.1-year follow-up. In Cox proportional hazard regression analysis, low levels of ApoA-I/IgG ICs were independent predictors of adverse cardiovascular outcomes after adjustment for age, sex, diabetes mellitus, estimated glomerular filtration rate, presence of obstructive CAD, heart failure, total cholesterol, and HDL (high-density lipoprotein) cholesterol (adjusted hazard ratio of 1.90 [95% CI, 1.03-3.49; P=0.038] between the lowest and the highest tertiles).
Low levels of ApoA-I/IgG ICs are associated with an increased risk of adverse events in patients with CAD, raising their potential to be used as a biomarker to predict CVD progression.
免疫反应与动脉粥样硬化性心血管疾病（CVD）的进展有关。已鉴定出针对载脂蛋白 A-I（载脂蛋白 A-I）的游离自身抗体是患者炎症环境的一个组成部分，并且与 CVD 进展具有中度相关性。基于这些抗体的存在和循环 ApoA-I 的高浓度，我们假设与 ApoA-I 结合作为免疫复合物的抗体将预测不良 CVD 结局的发生。
通过 ELISA 在 3 个研究对象队列中证实了血浆中 ApoA-I/IgG 免疫复合物（IC）的存在。对 ApoAI/IgG IC 中蛋白质成分的特征分析表明，IC 与总 ApoA-I 浓度无关，与总血浆 IgG 相比，IC 富含抗炎亚类 IgG4（>30%对 6%）。在 359 例冠心病（CAD）患者中，中位随访 4.1 年后有 71 例发生不良 CVD 事件（死亡、心肌梗死和中风）。在 Cox 比例风险回归分析中，在校正年龄、性别、糖尿病、估计肾小球滤过率、存在阻塞性 CAD、心力衰竭、总胆固醇和高密度脂蛋白（HDL）胆固醇后，ApoA-I/IgG IC 水平低是不良心血管结局的独立预测因子（最低和最高三分位数之间的调整危险比为 1.90 [95%CI，1.03-3.49；P=0.038]）。
在 CAD 患者中，ApoA-I/IgG IC 水平低与不良事件风险增加相关，这提高了其作为预测 CVD 进展的生物标志物的潜力。
