Xiao Dangsheng, Wang Ju, Chen Zhitao, Jin Xiuyuan, Xie Yirui, Yan Dong, Yang Jiezuan
Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, Department of Geriatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310003, Hangzhou, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310003, Hangzhou, China.
BMC Infect Dis. 2021 Jan 23;21(1):111. doi: 10.1186/s12879-021-05816-2.
T cells play an important role in the prognosis of hepatitis B virus (HBV) infection, and are involved in the seroconversion of a patient from HBsAb negative to positive. To compare the T-cell receptor β-chain variable region (TcRBV) complementarity-determining region 3 (CDR3) in subjects with or without hepatitis B surface antigen (HBsAg) convert to hepatitis B surface antibody (HBsAb), the TcRBV was determined using high throughput sequencing (HTS).
The clonotype and diversity of CDR3 in peripheral blood mononuclear cells of subjects with resolved acute hepatitis B (AHB, HBsAb+, HBsAg-) (n = 5), chronic hepatitis B (CHB, HBsAb-, HBsAg+) (n = 5), and healthy controls (HC, HBsAb-, HBsAg-) (n = 3) were determined and analyzed using HTS (MiSeq).
The overlapping rate of CDR3 clones of any two samples in AHB group was 2.00% (1.74% ~ 2.30%), CHB group was 1.77% (1.43% ~ 2.61%), and HC group was 1.82% (1.62% ~ 2.12%), and there was no significant difference among the three groups by Kruskal-Wallis H test. However, among the top 10 cumulative frequencies of clonotypes, only the frequency of clonotype (TcRBV20-1/BD1/BJ1-2) in AHB group was lower than that of HC group (P < 0.001). Moreover, exclude the 10 top clonotypes, there are 57 markedly different frequency of clones between AHB and CHB groups (18 clones up, 39 clones down), 179 (180-1) different clones between AHB and HC groups, and 134 different clones between CHB and HC groups. With regard to BV and BJ genotypes, there was no significant different frequency among the groups. Furthermore, there was no significant difference in the diversity of TcRBV CDR3 among the three groups (P > 0.05).
Thus, there are 57 TcRBV clonotypes that may be related to HBsAg seroconversion of AHB subjects, but the diversity of TcRBV CDR3 is not significantly related to the HBsAb positive status.
T细胞在乙型肝炎病毒（HBV）感染的预后中起重要作用，并参与患者从乙肝表面抗体（HBsAb）阴性转为阳性的血清学转换。为比较有或无乙肝表面抗原（HBsAg）转换为乙肝表面抗体（HBsAb）的受试者的T细胞受体β链可变区（TcRBV）互补决定区3（CDR3），采用高通量测序（HTS）测定TcRBV。
使用HTS（MiSeq）测定并分析急性乙型肝炎康复者（AHB，HBsAb+，HBsAg-）（n = 5）、慢性乙型肝炎患者（CHB，HBsAb-，HBsAg+）（n = 5）和健康对照者（HC，HBsAb-，HBsAg-）（n = 3）外周血单个核细胞中CDR3的克隆型和多样性。
AHB组任意两个样本的CDR3克隆重叠率为2.00%（1.74%～2.30%），CHB组为1.77%（1.43%～2.61%），HC组为1.82%（1.62%～2.12%），Kruskal-Wallis H检验显示三组间无显著差异。然而，在克隆型的前10个累积频率中，仅AHB组克隆型（TcRBV20-1/BD1/BJ1-2）的频率低于HC组（P < 0.001）。此外，排除前10个克隆型后，AHB组和CHB组之间有57个克隆频率明显不同（18个克隆频率升高，39个克隆频率降低），AHB组和HC组之间有179个（180 - 1）不同克隆，CHB组和HC组之间有134个不同克隆。关于BV和BJ基因型，各组间频率无显著差异。此外，三组间TcRBV CDR3的多样性无显著差异（P > 0.05）。
因此，有57种TcRBV克隆型可能与AHB受试者的HBsAg血清学转换有关，但TcRBV CDR3的多样性与HBsAb阳性状态无显著相关性。
