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三氯乙烯所致职业性似药疹样皮炎患者外周血 TCR β 链 CDR3 repertoire 的动态分析。

Dynamic analysis of peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene.

机构信息

Medical Laboratory, Shenzhen Prevention and Treatment Center for Occupational Diseases, 2019 Buxin Rd., Luohu district, Shenzhen, 518020, China.

Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.

出版信息

Sci Rep. 2021 May 11;11(1):9971. doi: 10.1038/s41598-021-89431-w.

Abstract

Previously, we had cross-sectionally explored the characteristics of T cell receptor (TCR) repertoires from occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) patients, now we further analyzed the dynamic features of OMDT TCR repertoires. Peripheral blood TCR β-chain complementarity-determining region 3 (CDR3) genes were detected with the high throughput sequencing in 24 OMDT cases in their acute, chronic and recovery stages, respectively, and in 24 trichloroethylene-exposed healthy controls. The TCR repertoire diversity, TRBV/TRBD/TRBJ gene usage and combination, frequencies of CDR3 nucleotide (nt) and amino acid (aa) sequences in the cases in different stages and in the controls were analyzed. TRBV6-4 and TRBV7-9 frequencies significantly differed between the cases and controls (both P < 6.1 × 10). TRBV6-4 combination with TRBJ2-1, TRBJ2-2, TRBJ2-3, and TRBJ2-6, and TRBV7-9 combination with TRBJ2-1 were associated with the stage by OMDT severity (all P < 0.001). Ten CDR3-nt and 7 CDR3-aa sequences in TRBV7-9-TRBJ2-1 combination and 1 CDR3-nt and 1 CDR3-aa sequences in TRBV6-4-TRBJ2-1 combination were identified as associated with the severity of OMDT (all P < 0.001). We revealed further how TCR repertoires vary with the severity in the development of OMDT, and severity-related TCRs may provide important therapeutic targets for OMDT in clinical practice.

摘要

先前,我们已经对职业性三氯乙烯药疹样皮炎(OMDT)患者的 T 细胞受体(TCR)库特征进行了横断面研究,现在我们进一步分析了 OMDT TCR 库的动态特征。分别对 24 例处于急性、慢性和恢复期的 OMDT 患者及 24 例三氯乙烯接触健康对照者外周血 TCR β 链互补决定区 3(CDR3)基因进行高通量测序,分析不同阶段病例和对照者 TCR 库多样性、TRBV/TRBD/TRBJ 基因使用及组合、CDR3 核苷酸(nt)和氨基酸(aa)序列频率。病例与对照者间 TRBV6-4 和 TRBV7-9 频率存在显著差异(均 P<6.1×10)。TRBV6-4 与 TRBJ2-1、TRBJ2-2、TRBJ2-3 和 TRBJ2-6 组合,TRBV7-9 与 TRBJ2-1 组合与 OMDT 严重程度相关(均 P<0.001)。TRBV7-9-TRBJ2-1 组合中有 10 个 CDR3-nt 和 7 个 CDR3-aa 序列,TRBV6-4-TRBJ2-1 组合中有 1 个 CDR3-nt 和 1 个 CDR3-aa 序列与 OMDT 严重程度相关(均 P<0.001)。我们进一步揭示了 TCR 库如何随 OMDT 严重程度而变化,与严重程度相关的 TCR 可能为 OMDT 的临床治疗提供重要的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a46/8113444/733d67db4a3f/41598_2021_89431_Fig1_HTML.jpg

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