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使用高通量测序分析蛛网膜下腔出血患者的T细胞受体β链互补决定区3库

Profiling of T Cell Receptor β-Chain Complimentary Determining Regions 3 Repertoire in Subarachnoid Hemorrhage Patients Using High-Throughput Sequencing.

作者信息

Kim Bong Jun, Ahn Jun Hyong, Youn Dong Hyuk, Jeon Jin Pyeong

机构信息

Institute of New Frontier Stroke Research, Hallym University College of Medicine, Chuncheon, Korea.

Department of Neurosurgery, Hallym University College of Medicine, Chuncheon, Korea.

出版信息

J Korean Neurosurg Soc. 2021 Jul;64(4):505-513. doi: 10.3340/jkns.2020.0214. Epub 2021 Jun 29.

Abstract

OBJECTIVE

The adaptive immune response following subarachnoid hemorrhage (SAH) is not well understood. We evaluated and compared the T cell receptor (TCR) immune repertoire of good-grade and poor-grade SAH patients to elucidate the T cell immunology after ictus.

METHODS

Peripheral blood from six SAH patients was collected at two different times, admission and at the 7-day follow-up. Composition and variation of the TCR β-chain (TCRB) complimentary determining regions (CDR) 3 repertoire was examined using high-throughput sequencing; the analysis was based on sampling time and disease severity (good vs. poor-grade SAH).

RESULTS

Clonality at admission and follow-up were 0.059 (0.037-0.038) and 0.027 (0.014-0.082) (median, 25th-75th percentile). Poor-grade SAH (0.025 [0.011-0.038]) was associated with significantly lower clonality than good-grade SAH (0.095 [0.079-0.101]). Poor-grade SAH patients had higher diversity scores than good-grade SAH patients. CDR length was shorter in good-grade SAH vs. poor-grade SAH. Differences in clonotype distribution were more prominent in TCRBV gene segments than TCRBJ segments. TCRBV19-01/TCRBJ02-04 and TCRBV28-01/TCRBJ02-04 were the most increased and the most decreased V-J pairs in the 7-day follow-up compared to admission in good-grade SAH. The most increased and decreased V-J pairs in poor-grade SAH patients were TCRBV28-01/TCRBJ02-06 and TCRBV30-01/TCRBJ02-04, respectively.

CONCLUSION

The TCRB repertoire is dynamic in nature following SAH. TCRB repertoire may facilitate our understanding of adaptive immune response according to SAH severity.

摘要

目的

蛛网膜下腔出血(SAH)后的适应性免疫反应尚未完全明确。我们评估并比较了病情较轻和较重的SAH患者的T细胞受体(TCR)免疫库,以阐明发病后的T细胞免疫学情况。

方法

收集6例SAH患者在两个不同时间点(入院时和7天随访时)的外周血。使用高通量测序检查TCRβ链(TCRB)互补决定区(CDR)3免疫库的组成和变化;分析基于采样时间和疾病严重程度(病情较轻与较重的SAH)。

结果

入院时和随访时的克隆性分别为0.059(0.037 - 0.038)和0.027(0.014 - 0.082)(中位数,第25 - 75百分位数)。病情较重的SAH(0.025 [0.011 - 0.038])与显著低于病情较轻的SAH(0.095 [0.079 - 0.101])的克隆性相关。病情较重的SAH患者的多样性得分高于病情较轻的SAH患者。病情较轻的SAH患者的CDR长度比病情较重的SAH患者短。克隆型分布的差异在TCRBV基因片段中比在TCRBJ片段中更突出。与入院时相比,病情较轻的SAH患者在7天随访中TCRBV19 - 01/TCRBJ02 - 04和TCRBV28 - 01/TCRBJ02 - 04是增加最多和减少最多的V - J对。病情较重的SAH患者中增加最多和减少最多的V - J对分别是TCRBV28 - 01/TCRBJ02 - 06和TCRBV30 - 01/TCRBJ02 - 04。

结论

SAH后TCRB免疫库本质上是动态的。TCRB免疫库可能有助于我们根据SAH严重程度理解适应性免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e3/8273768/b9481bf6265c/jkns-2020-0214f1.jpg

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