在慢性乙型肝炎患者中，循环血清HBsAg水平是HBV特异性T和B细

StephenW

Sci Rep. 2020 Feb 4;10(1):1835. doi: 10.1038/s41598-020-58870-2.
Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients.
Kim JH1, Ghosh A2, Ayithan N2, Romani S2, Khanam A2, Park JJ1, Rijnbrand R1, Tang L2, Sofia MJ1, Kottilil S2, Moore CB1, Poonia B3.
Author information

1
    Arbutus Biopharma Corporation, 701 Veterans Circle, Warminster, Pennsylvania, 18974, United States.
2
    Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, United States.
3
    Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, United States. [email protected].

Abstract

Chronic hepatitis B (CHB) infection functional cure is defined as sustained loss of HBsAg and several therapeutic strategies are in clinical development designed to pharmacologically reduce serum HBsAg, break immune tolerance, and increase functional cure rates. However, little is known about pre-treatment HBsAg levels as an indicator of HBV immune potential. Here, we compared the phenotypes and HBV-specific response of lymphocytes in CHB patients stratified by serum HBsAg levels <500 (HBslo) or >50,000 IU/ml (HBshi) using immunological assays (flow cytometry, ICS, ELISPOT). HBshi patients had significantly higher expression of inhibitory PD-1 on CD4+ T cells, particularly among TEMRA subset, and higher FcRL5 expression on B cells. Upon HBcAg(core) or HBsAg(env)-stimulation, 85% and 60% of HBslo patients had IFNγ+TNFα+ and IFNγ+ IL2+ CD4+ T cell responses respectively, in comparison to 33% and 13% of HBshi patients. Checkpoint blockade with αPD-1 improved HBV-specific CD4+ T cell function only in HBslo patients. HBsAg-specific antibody-secreting cells (ASCs) response was not different between these groups, yet αPD-1 treatment resulted in significantly higher fold change in ASCs among patients with HBsAg <100 IU/ml compared to patients with HBsAg >5,000 IU/ml. Thus, serum HBsAg correlates with inhibitory receptor expression, HBV-specific CD4+ T cell responses, and augmentation by checkpoint blockade.

PMID:
    32020034
DOI:
    10.1038/s41598-020-58870-2

StephenW

Sci Rep.2020年2月4日； 10（1）：1835。 doi：10.1038 / s41598-020-58870-2。
在慢性乙型肝炎患者中，循环血清HBsAg水平是HBV特异性T和B细胞反应的生物标志物。
Kim JH1，Ghosh A2，Ayithan N2，Romani S2，Khanam A2，Park JJ1，Rijnbrand R1，Tang L2，Sofia MJ1，Kottilil S2，Moore CB1，Poonia B3。
作者信息

1个
    Arbutus Biopharma Corporation，701退伍军人圈，沃明斯特，宾夕法尼亚州，18974，美国。
2
    马里兰大学医学院人类病毒研究所，马里兰州巴尔的摩，美国21201。
3
    马里兰大学医学院人类病毒研究所，马里兰州巴尔的摩，美国21201。 [email protected]。

抽象

慢性乙型肝炎（CHB）感染的功能性治愈被定义为HBsAg的持续丧失，并且在临床开发中，有几种治疗策略被设计为以药理学的方式降低血清HBsAg，破坏免疫耐受性并提高功能性治愈率。但是，对于治疗前HBsAg水平作为HBV免疫潜能指标的了解甚少。在这里，我们使用免疫学分析（流式细胞仪，ICS，ELISPOT）比较了血清HBsAg水平<500（HBslo）或> 50,000 IU / ml（HBshi）分层的CHB患者淋巴细胞的表型和HBV特异性应答。 HBshi患者在CD4 + T细胞上具有较高的抑制性PD-1表达，特别是在TEMRA亚组中，在B细胞上具有较高的FcRL5表达。 HBcAg（核心）或HBsAg（env）刺激后，分别有85％和60％的HBslo患者具有IFNγ+TNFα+和IFNγ+ IL2 + CD4 + T细胞反应，而HBshi患者分别为33％和13％。仅在HBslo患者中，用αPD-1进行的检查点封锁可改善HBV特异性CD4 + T细胞功能。这些组之间的HBsAg特异性抗体分泌细胞（ASCs）反应无差异，但是与HBsAg> 5,000 IU / ml的患者相比，αPD-1治疗导致HBsAg <100 IU / ml的患者的ASC倍数变化明显更高。因此，血清HBsAg与抑制性受体表达，HBV特异性CD4 + T细胞反应以及通过检查点封锁而增加有关。

PMID：
    32020034
DOI：
    10.1038 / s41598-020-58870-2

StephenW

https://www.nature.com/articles/s41598-020-58870-2.pdf