Comprehensive assessment of peripheral blood TCRβ repertoire in infectious mononucleosis and chronic active EBV infection patients
Comprehensive assessment of peripheral blood TCRβ repertoire in infectious mononucleosis and chronic active EBV infection patients
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传染性单核细胞增多症和慢性活动性EBV感染患者外周血TCRβ谱的综合评估
DOI：
10.1007/s00277-016-2911-8
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发表时间：
2017-04-01
影响因子：
3.5
通讯作者：
Zhang, Hongyu
中科院分区：
文献类型：
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作者：
Liu, Shenglin;Zhang, Qian;Zhang, Hongyu
EB病毒（EBV）原发性感染通常无症状，但有时会发展为传染性单核细胞增多症（IM）。偶尔，一些人发展为慢性活动性EBV感染（CAEBV），伴有潜在的免疫缺陷，属于EBV相关淋巴组织增生性疾病（EBV+ LPD）的连续谱，具有异质性临床表现和高死亡率。已经确定T细胞介导的免疫应答在EBV感染的疾病演变中起关键作用。最近，T细胞受体（T细胞受体β（TCR β））的高变互补决定区3（CDR 3）区段的高通量测序已经成为评估T细胞库的敏感方法。在这项研究中，我们充分表征了IM（n = 6）和CAEBV患者（n = 5）以及EBV血清阳性对照（n = 5）中外周血TCR β库的多样性。与健康EBV血清阳性对照相比，IM和CAEBV患者均表现出外周血TCR β库多样性的显著降低，基本上包括库宽度变窄、克隆高度扩增和CDR 3长度分布偏斜。然而，IM和CAEBV患者之间没有显著差异。此外，我们观察到TRBV/TRBJ使用和组合中的一些疾病相关偏好，以及参与公共T细胞应答的不同群体（独特或重叠）共享的大量T细胞克隆，这为不同的疾病演变提供了更详细的见解。
Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV+ LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor beta (TCR beta)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCR beta repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCR beta repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution.