Weng Ruiqiang, Liu Sudong, Gu Xiaodong, Zhong Zhixiong
Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People's Republic of China.
Guangdong Provincial Engineering and Technological Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, 514031, People's Republic of China.
Genes Genomics. 2022 Jan;44(1):19-28. doi: 10.1007/s13258-021-01110-2. Epub 2021 May 11.
Acute coronary syndrome (ACS) is a complex cardiovascular disease whose development involves the dysregulation of adaptive immune responses. Though it has been proven that T cells associate with inflammation in the development of ACS, the function of B cells in disease remains unclear.
The aim of this study was to reveal the diversity of the B cell receptor (BCR) repertoire of patients with ACS.
We conducted a pilot study to sequence the immune repertoire of peripheral blood mononuclear cells (PBMCs) from patients with ACS, including acute myocardial infarction (AMI) and unstable angina (UA), and quantitatively characterized BCR repertoires by bioinformatics analysis.
We found that patients with AMI and UA had lower BCR repertoire diversity compared with controls with normal coronary arteries (NCA). Lower percentages of productive unique BCR nt sequences and higher percentages of top 200 unique BCR sequences were identified in AMI and UA patients than NCA controls. Patients had various preferential usage of V and J genes from B cell clones in accordance with the disease severity of coronary arteries. AMI patients had distinct CDR3 amino acids, and their frequency differed among patients with ACS.
Our results indicate that differential BCR signatures represent an imprint of distinct repertoires among ACS patients. This study thereby opens up the prospect of studying disease-relevant B cells to better understand and treat ACS.
急性冠状动脉综合征(ACS)是一种复杂的心血管疾病,其发展涉及适应性免疫反应的失调。尽管已证实T细胞在ACS发展过程中与炎症相关,但B细胞在该疾病中的功能仍不清楚。
本研究旨在揭示ACS患者B细胞受体(BCR)库的多样性。
我们进行了一项初步研究,对ACS患者(包括急性心肌梗死(AMI)和不稳定型心绞痛(UA))外周血单个核细胞(PBMC)的免疫库进行测序,并通过生物信息学分析对BCR库进行定量表征。
我们发现,与冠状动脉正常(NCA)的对照组相比,AMI和UA患者的BCR库多样性较低。与NCA对照组相比,AMI和UA患者中具有功能的独特BCR核苷酸序列百分比更低,而前200个独特BCR序列的百分比更高。根据冠状动脉疾病的严重程度,患者的B细胞克隆对V和J基因有不同的优先使用情况。AMI患者具有独特的互补决定区3(CDR3)氨基酸,且其频率在ACS患者中存在差异。
我们的结果表明,不同的BCR特征代表了ACS患者中不同库的印记。因此,本研究为研究与疾病相关的B细胞以更好地理解和治疗ACS开辟了前景。