Department of Chemistry, Stanford University, Stanford, CA 94305.
Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven 3000, Belgium.
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7089-7094. doi: 10.1073/pnas.1621457114. Epub 2017 Jun 19.
The role of autoimmunity in cardiovascular (CV) diseases has been increasingly recognized. Autoimmunity is most commonly examined by the levels of circulating autoantibodies in clinical practices. Measurement of autoantibodies remains, however, challenging because of the deficiency of reproducible, sensitive, and standardized assays. The lack of multiplexed assays also limits the potential to identify a CV-specific autoantibody profile. To overcome these challenges, we developed a nanotechnology-based plasmonic gold chip for autoantibody profiling. This approach allowed simultaneous detection of 10 CV autoantibodies targeting the structural myocardial proteins, the neurohormonal regulatory proteins, the vascular proteins, and the proteins associated with apoptosis and coagulation. Autoantibodies were measured in four groups of participants across the continuum of hypertensive heart diseases. We observed higher levels of all 10 CV autoantibodies in hypertensive subjects ( = 77) compared with healthy participants ( = 30), and the autoantibodies investigated were related to each other, forming a highly linked network. In addition, we established that autoantibodies to troponin I, annexin-A5, and beta 1-adrenegic receptor best discriminated hypertensive subjects with adverse left ventricular (LV) remodeling or dysfunction ( = 49) from hypertensive subjects with normal LV structure and function ( = 28). By further linking these three significant CV autoantibodies to the innate and growth factors, we revealed a positive but weak association between autoantibodies to troponin I and proinflammatory cytokine IL-18. Overall, we demonstrated that this platform can be used to evaluate autoantibody profiles in hypertensive subjects at risk for heart failure.
自身免疫在心血管(CV)疾病中的作用已越来越受到重视。在临床实践中,通常通过循环自身抗体的水平来检查自身免疫。然而,由于缺乏可重复、敏感和标准化的检测方法,测量自身抗体仍然具有挑战性。缺乏多重检测方法也限制了识别特定于 CV 的自身抗体谱的潜力。为了克服这些挑战,我们开发了一种基于纳米技术的等离子金芯片来进行自身抗体分析。该方法允许同时检测针对结构心肌蛋白、神经激素调节蛋白、血管蛋白以及与细胞凋亡和凝血相关的蛋白的 10 种 CV 自身抗体。我们在高血压心脏病连续体的四个参与者组中测量了自身抗体。与健康参与者(n = 30)相比,我们观察到高血压患者(n = 77)的所有 10 种 CV 自身抗体水平均较高,并且所研究的自身抗体相互关联,形成了一个高度关联的网络。此外,我们确定了肌钙蛋白 I、膜联蛋白-A5 和β1-肾上腺素能受体的自身抗体可最好地区分左心室(LV)重构或功能障碍不良的高血压患者(n = 49)与 LV 结构和功能正常的高血压患者(n = 28)。通过进一步将这三种重要的 CV 自身抗体与先天和生长因子联系起来,我们发现肌钙蛋白 I 的自身抗体与促炎细胞因子 IL-18 之间存在正相关但较弱的关联。总体而言,我们证明了该平台可用于评估处于心力衰竭风险中的高血压患者的自身抗体谱。