Table2_RNAseq of INOCA patients identifies innate, invariant, and acquired immune changes: potential autoimmune microvascular dysfunction.xlsx

BackgroundIschemia with non-obstructive coronary arteries (INOCA) is a major clinical entity that involves potentially 20%–30% of patients with chest pain. INOCA is typically attributed either to coronary microvascular disease and/or vasospasm, but is likely distinct from classical coronary artery disease (CAD).
ObjectivesTo gain insights into the etiology of INOCA and CAD, RNA sequencing of whole blood from patients undergoing both stress testing and elective invasive coronary angiography (ICA) was conducted.
MethodsStress testing and ICA of 177 patients identified 40 patients (23%) with INOCA compared to 39 controls (stress-, ICA-). ICA+ patients divided into 38 stress- and 60 stress+. RNAseq was performed by Illumina with ribosomal RNA depletion. Transcriptome changes were analyzed by DeSeq2 and curated by manual and automated methods.
ResultsDifferentially expressed genes for INOCA were associated with elevated levels of transcripts related to mucosal-associated invariant T (MAIT) cells, plasmacytoid dendritic cells (pcDC), and memory B cells, and were associated with autoimmune diseases such as rheumatoid arthritis. Decreased transcripts were associated with neutrophils, but neutrophil transcripts, per se, were not less abundant in INOCA. CAD transcripts were more related to T cell functions.
ConclusionsElevated transcripts related to pcDC, MAIT, and memory B cells suggest an autoimmune component to INOCA. Reduced neutrophil transcripts are likely attributed to chronic activation leading to increased translation and degradation. Thus, INOCA could result from stimulation of B cell, pcDC, invariant T cell, and neutrophil activation that compromises cardiac microvascular function.

背景 非阻塞性冠状动脉缺血（Ischemia with Non-Obstructive Coronary Arteries, INOCA）是一类重要的临床病症，约累及20%~30%的胸痛患者。INOCA通常归因于冠状动脉微血管疾病和/或血管痉挛，但大概率有别于经典冠状动脉粥样硬化性心脏病（Coronary Artery Disease, CAD）。
目的 为深入探究非阻塞性冠状动脉缺血（INOCA）与冠状动脉粥样硬化性心脏病（CAD）的发病机制，本研究对同时接受负荷试验与择期有创冠状动脉造影（Invasive Coronary Angiography, ICA）的患者的全血进行了RNA测序。
方法 本研究对177例患者实施负荷试验与有创冠状动脉造影后，确诊40例（23%）非阻塞性冠状动脉缺血患者，同时纳入39例对照者（负荷试验阴性、有创冠状动脉造影阴性）。有创冠状动脉造影阳性患者分为38例负荷试验阴性者与60例负荷试验阳性者。RNA测序（RNAseq）由Illumina平台完成，采用核糖体RNA去除建库策略。转录组差异变化通过DeSeq2进行分析，并通过人工与自动化结合的方式完成数据整理。
结果 非阻塞性冠状动脉缺血患者的差异表达基因与黏膜相关恒定T（Mucosal-Associated Invariant T, MAIT）细胞、浆细胞样树突状细胞（plasmacytoid dendritic cells, pcDC）以及记忆B细胞相关转录本的水平升高存在关联，同时与类风湿关节炎等自身免疫性疾病相关。转录本水平降低的基因与中性粒细胞相关，但中性粒细胞本身的转录本在非阻塞性冠状动脉缺血患者中并未出现丰度下降。冠状动脉粥样硬化性心脏病相关的转录本则更多与T细胞功能相关。
结论 与浆细胞样树突状细胞、黏膜相关恒定T细胞以及记忆B细胞相关的转录本水平升高，提示非阻塞性冠状动脉缺血存在自身免疫相关的发病机制。中性粒细胞相关转录本水平降低，可能源于慢性活化导致翻译与降解过程增强。综上，非阻塞性冠状动脉缺血可能由B细胞、浆细胞样树突状细胞、恒定T细胞以及中性粒细胞的活化刺激引发，进而损害心脏微血管功能。