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高通量测序分析急性冠脉综合征患者 T 细胞受体库。

Comprehensive analysis of T-cell receptor repertoire in patients with acute coronary syndrome by high-throughput sequencing.

机构信息

Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China.

Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, P. R. China.

出版信息

BMC Cardiovasc Disord. 2020 May 27;20(1):253. doi: 10.1186/s12872-020-01538-6.

DOI:10.1186/s12872-020-01538-6
PMID:32460698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7254720/
Abstract

BACKGROUND

This study aims to investigate the T-cell receptor (TCR) repertoire in patients with acute coronary syndrome (ACS).

METHODS

The TCR repertoires of 9 unstable angina patients (UA), 14 acute myocardial infarction patients (AMI) and 9 normal coronary artery (NCA) patients were profiled using high-throughput sequencing (HTS). The clonal diversity of the TCR repertoires in different groups was analyzed, as well as the frequencies of variable (V), diversity (D) and joining(J) gene segments.

RESULTS

ACS patients including UA and AMI, showed reduced TCRβ diversity than NCA patients. ACS patients presented higher levels of clonal expansion. The clonotype overlap of complementarity determining region 3(CDR3) was significantly varied between different groups. A total of 10 V genes and 1 J gene were differently utilized between ACS and NCA patients. We identified some shared CDR3 amino acid sequences that were presented in ACS but not in NCA patients.

CONCLUSIONS

This study revealed the distinct TCR repertoires in patients with ACS and demonstrated the presence of disease associated T-cell clonotypes. These findings suggested a role of T cells in ACS and provided a new way to explore the mechanisms of ACS.

摘要

背景

本研究旨在探讨急性冠状动脉综合征(ACS)患者的 T 细胞受体(TCR)库。

方法

采用高通量测序(HTS)对 9 例不稳定型心绞痛(UA)患者、14 例急性心肌梗死(AMI)患者和 9 例正常冠状动脉(NCA)患者的 TCR 库进行分析。分析不同组 TCR 库的克隆多样性,以及可变(V)、多样性(D)和连接(J)基因片段的频率。

结果

ACS 患者(包括 UA 和 AMI)的 TCRβ多样性低于 NCA 患者。ACS 患者表现出更高的克隆扩增水平。不同组之间互补决定区 3(CDR3)的克隆型重叠明显不同。ACS 和 NCA 患者之间共有 10 个 V 基因和 1 个 J 基因存在差异。我们确定了一些在 ACS 患者中存在但在 NCA 患者中不存在的共享 CDR3 氨基酸序列。

结论

本研究揭示了 ACS 患者中独特的 TCR 库,并证实了与疾病相关的 T 细胞克隆型的存在。这些发现提示 T 细胞在 ACS 中的作用,并为探索 ACS 的机制提供了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/0bbfd369034c/12872_2020_1538_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/03c2f4abfd35/12872_2020_1538_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/c91f02178807/12872_2020_1538_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/903d4608db6a/12872_2020_1538_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/0bbfd369034c/12872_2020_1538_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/03c2f4abfd35/12872_2020_1538_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/c91f02178807/12872_2020_1538_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/903d4608db6a/12872_2020_1538_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ab0/7254720/0bbfd369034c/12872_2020_1538_Fig4_HTML.jpg

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Deep sequencing of the T cell receptor β repertoire reveals signature patterns and clonal drift in atherosclerotic plaques and patients.T细胞受体β库的深度测序揭示了动脉粥样硬化斑块和患者中的特征模式及克隆漂移。
Oncotarget. 2017 Aug 3;8(59):99312-99322. doi: 10.18632/oncotarget.19892. eCollection 2017 Nov 21.
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Oncoimmunology. 2016 Aug 5;5(10):e1219010. doi: 10.1080/2162402X.2016.1219010. eCollection 2016.
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