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慢性乙型肝炎患者中同时存在乙肝表面抗原(HBsAg)和乙肝表面抗体(抗-HBs)时的T细胞受体β链和B细胞受体库

T-Cell Receptor β Chain and B-Cell Receptor Repertoires in Chronic Hepatitis B Patients with Coexisting HBsAg and Anti-HBs.

作者信息

Zhan Qiao, Chang Le, Wu Jian, Zhang Zhiyuan, Xu Jinghang, Yu Yanyan, Feng Zhenru, Zeng Zheng

机构信息

Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.

Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034, China.

出版信息

Pathogens. 2022 Jun 26;11(7):727. doi: 10.3390/pathogens11070727.

DOI:10.3390/pathogens11070727
PMID:35889974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9318409/
Abstract

Antibodies in response to antigens are related to the immune repertoire of T- and B-cell receptors. However, some patients with chronic hepatitis B (CHB) have coexisting HBsAg and anti-HBsAg antibodies (anti-HBs) that cannot neutralize HBV. We attempted to investigate the repertoires that produce this response in CHB patients. The T-cell receptor β chain (TRB) and B-cell receptor (BCR) repertoires of peripheral blood genomic DNA were analyzed using MiXCR. T-cell receptor (TCR) cluster analysis was carried out by clusTCR, and motifs prediction was selected by Multiple Em for Motif Elicitation (MEME). A total of 76 subjects were enrolled, including 26 HBsAg and anti-HBs coexisting patients with CHB (DP group), 25 anti-HBs single-positive healthy people (SP group), and 25 CHB patients (CHB group). The clone length of BCR in 39, 90 was significantly different among these groups ( = 0.005, 0.036). The motif "CASSLG" in the DP group was significantly higher than SP and CHB groups and may relate to coexistence, and the motif "GAGPLT" was only shown in the SP group and may relate to anti-HB expression. These provide important insights into vaccine development and CHB treatment.

摘要

针对抗原产生的抗体与T细胞和B细胞受体的免疫库有关。然而,一些慢性乙型肝炎(CHB)患者同时存在乙肝表面抗原(HBsAg)和不能中和乙肝病毒(HBV)的抗HBsAg抗体(抗-HBs)。我们试图研究慢性乙肝患者中产生这种反应的免疫库。使用MiXCR分析外周血基因组DNA的T细胞受体β链(TRB)和B细胞受体(BCR)免疫库。通过clusTCR进行T细胞受体(TCR)聚类分析,并通过多重期望最大化(MEME)选择基序预测。共纳入76名受试者,包括26名HBsAg和抗-HBs共存的慢性乙肝患者(DP组)、25名抗-HBs单阳性健康人(SP组)和25名慢性乙肝患者(CHB组)。这些组中BCR的克隆长度在39、90处有显著差异(P = 0.005,0.036)。DP组中的基序“CASSLG”显著高于SP组和CHB组,可能与共存有关,而基序“GAGPLT”仅在SP组中出现,可能与抗-HB表达有关。这些为疫苗开发和慢性乙肝治疗提供了重要见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/ecc0c5999f4c/pathogens-11-00727-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/e613a9416350/pathogens-11-00727-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/8d1d3a27b13b/pathogens-11-00727-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/6f81600603b1/pathogens-11-00727-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/056e9841b483/pathogens-11-00727-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/beede40fe27e/pathogens-11-00727-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/8eb13c9bd0b5/pathogens-11-00727-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/ecc0c5999f4c/pathogens-11-00727-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/e613a9416350/pathogens-11-00727-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/8d1d3a27b13b/pathogens-11-00727-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/6f81600603b1/pathogens-11-00727-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/056e9841b483/pathogens-11-00727-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/beede40fe27e/pathogens-11-00727-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/8eb13c9bd0b5/pathogens-11-00727-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/9318409/ecc0c5999f4c/pathogens-11-00727-g007.jpg

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