乙型肝炎表面抗原对慢性乙型肝炎病毒感染患者病毒特异性T

StephenW

Effects of Hepatitis B Surface Antigen on Virus-Specific and Global T Cells in Patients With Chronic Hepatitis B Virus infection

    Nina Le Bert ∗
    Upkar S. Gill ∗
    Michelle Hong ∗
    Evan W. Newell
    Patrick T.F. Kennedy §
    Antonio Bertoletti §
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Published:April 14, 2020DOI:https://doi.org/10.1053/j.gastro.2020.04.019
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Background & Aims
Chronic hepatitis B virus (HBV) infection is characterized by the presence of defective viral envelope proteins (hepatitis B surface antigen [HBsAg]) and the duration of infection—most patients acquire the infection at birth or during the first years of life. We investigated the effects of these factors on patients’ lymphocyte and HBV-specific T-cell populations.
Methods
We collected blood samples and clinical data from 243 patients with HBV infection (3–75 years old) in the United Kingdom and China. We measured levels of HBV DNA, HBsAg, hepatitis B e antigen, and alanine aminotransferase; analyzed HBV genotypes; and isolated peripheral blood mononuclear cells (PBMCs). In PBMCs from 48 patients with varying levels of serum HBsAg, we measured 40 markers on nature killer and T cells by mass cytometry. PBMCs from 189 patients with chronic infection and 38 patients with resolved infections were incubated with HBV peptide libraries, and HBV-specific T cells were identified by interferon gamma enzyme-linked immune absorbent spot (ELISpot) assays or flow cytometry. We used multivariate linear regression and performed variable selection using the Akaike information criterion to identify covariates associated with HBV-specific responses of T cells.
Results
Although T- and natural killer cell phenotypes and functions did not change with level of serum HBsAg, numbers of HBs-specific T cells correlated with serum levels of HBsAg ( r = 0.3367; P < .00001). After we performed the variable selection, the multivariate linear regression model identified patient age as the only factor significantly associated with numbers of HBs-specific T cells ( P = .000115). In patients younger than 30 years, HBs-specific T cells constituted 28.26% of the total HBV-specific T cells; this value decreased to 7.14% in patients older than 30 years.
Conclusions
In an analysis of immune cells from patients with chronic HBV infection, we found that the duration of HBsAg exposure, rather than the quantity of HBsAg, was associated with the level of anti-HBV immune response. Although the presence of HBs-specific T cells might not be required for the clearance of HBV infection in all patients, strategies to restore anti-HBV immune responses should be considered in patients younger than 30 years.

StephenW

乙型肝炎表面抗原对慢性乙型肝炎病毒感染患者病毒特异性T细胞和全局T细胞的影响

    妮娜·勒·伯特*
    Upkar S.Gill *
    香雪*
    埃文·纽维尔（Evan W.Newell）
    帕特里克·T·F肯尼迪§
    安东尼奥·贝托莱蒂§
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发布时间：2020年4月14日DOI：https：//doi.org/10.1053/j.gastro.2020.04.019
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背景与目标
慢性乙型肝炎病毒（HBV）感染的特征在于存在有缺陷的病毒包膜蛋白（乙型肝炎表面抗原[HBsAg]）和感染时间长短-大多数患者在出生时或生命的最初几年就感染了这种病毒。我们研究了这些因素对患者淋巴细胞和HBV特异性T细胞群体的影响。
方法
我们从英国和中国的243例HBV感染患者（3至75岁）中收集了血液样本和临床数据。我们测量了HBV DNA，HBsAg，乙型肝炎e抗原和丙氨酸转氨酶的水平。分析HBV基因型；和分离的外周血单个核细胞（PBMC）。在来自48名血清HBsAg水平不同的患者的PBMC中，我们通过质谱检测了40种自然杀伤和T细胞标记。将来自189例慢性感染患者和38例已解决感染患者的PBMC与HBV肽文库一起孵育，并通过干扰素γ酶联免疫吸附斑点（ELISpot）分析或流式细胞仪鉴定HBV特异性T细胞。我们使用多元线性回归并使用Akaike信息标准进行变量选择，以识别与T细胞的HBV特异性反应相关的协变量。
结果
尽管T细胞和自然杀伤细胞的表型和功能并未随血清HBsAg的水平而变化，但HBs特异性T细胞的数量与血清HBsAg的水平相关（r = 0.3367； P <.00001）。在我们执行变量选择之后，多元线性回归模型将患者年龄确定为与HBs特异性T细胞数量显着相关的唯一因素（P = .000115）。在30岁以下的患者中，HBs特异性T细胞占总HBV特异性T细胞的28.26％。在30岁以上的患者中，该值降至7.14％。
结论
在对来自慢性HBV感染患者的免疫细胞的分析中，我们发现HBsAg暴露的持续时间而不是HBsAg的数量与抗HBV免疫反应的水平有关。尽管并非所有患者都需要存在HBs特异性T细胞来清除HBV感染，但对于30岁以下的患者，应考虑恢复抗HBV免疫反应的策略。