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深度靶向测序揭示子痫前期患者 TRB-CDR3 库的多样性。

Deep targeted sequencing reveals the diversity of TRB-CDR3 repertoire in patients with preeclampsia.

机构信息

Department of Genetics, National Research Institute for Family Planning, Beijing 100081, China.

The First Affiliated Hospital, Medical College of Shantou University, Shantou, Guangdong 515041, China.

出版信息

Hum Immunol. 2019 Oct;80(10):848-854. doi: 10.1016/j.humimm.2019.04.003. Epub 2019 Apr 6.

Abstract

Preeclampsia (PE) is one of the major causes of maternal and perinatal mortality worldwide. This study aimed to determine the immunological characteristics of PE patients and normal pregnancy at the T cell receptor beta-chain (TRB) level by using high-throughput sequencing. High-throughput sequencing was performed to analyze the expression of TRB-CDR3 in circulating T cells. T cells were isolated from 36 healthy pregnant women, 24 patients with severe PE, and 18 patients with moderate PE. Rearranged mRNA sequences were assigned to their germline V, D, and J counterparts, and translated into proper amino acids by the IMGT database. In general, PE samples had more TRB-CDR3 reads and types than those of normal pregnant woman in the circulation, but the mean number of TRB-CDR3 reads and unique TRB-CDR3 reads in severe group was lower than that in the moderate group. In PE patients, the V7_9 and V20_1 gene loci were more prevalent than in healthy pregnant women. In addition, 4 kinds of TRB-CDR3 peptides were found to be highly relevant to the pathogenesis of PE. Of them, peptides matched to herpes simplex virus antigen-specific T cells were much lower in PE samples.

摘要

子痫前期 (PE) 是全球孕产妇和围生儿死亡的主要原因之一。本研究旨在通过高通量测序确定 PE 患者和正常妊娠在 T 细胞受体β链 (TRB) 水平的免疫学特征。通过高通量测序分析循环 T 细胞中 TRB-CDR3 的表达。从 36 名健康孕妇、24 名重度 PE 患者和 18 名中度 PE 患者中分离出 T 细胞。重排的 mRNA 序列被分配到其胚系 V、D 和 J 对应物,并通过 IMGT 数据库翻译成适当的氨基酸。一般来说,PE 样本在循环中比正常孕妇具有更多的 TRB-CDR3 读数和类型,但重度组的 TRB-CDR3 读数平均值和独特的 TRB-CDR3 读数低于中度组。在 PE 患者中,V7_9 和 V20_1 基因座比健康孕妇更常见。此外,发现 4 种 TRB-CDR3 肽与 PE 的发病机制高度相关。其中,与单纯疱疹病毒抗原特异性 T 细胞匹配的肽在 PE 样本中明显降低。

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