乙型肝炎病毒特异性T细胞与核苷（酸）类似物治疗中止时的

StephenW

Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation        
Laura Rivino,1 Nina Le Bert,1,2 Upkar S. Gill,1,3 Kamini Kunasegaran,1 Yang Cheng,4 Damien Z.M. Tan,2 Etienne Becht,4 Navjyot K. Hansi,3 Graham R. Foster,3 Tung-Hung Su,5 Tai-Chung Tseng,5 Seng Gee Lim,6 Jia-Horng Kao,5 Evan W. Newell,4 Patrick T.F. Kennedy,3 and Antonio Bertoletti1,2,4                                                                                                                              

First published January 8, 2018

See the related Commentary at Unravelling the fate of functional PD1+ T cells in chronic viral hepatitis.

                        AbstractBACKGROUND. The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which patients nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, therapy discontinuation can be associated with virological and biochemical relapse and, consequently, therapy in the majority is life-long.
METHODS. Since antiviral immunity is pivotal for HBV control, we investigated potential biomarkers for the safe discontinuation of NUCs within immune profiles of chronic HBV patients by utilizing traditional immunological assays (ELISPOT, flow cytometry) in conjunction with analyses of global non–antigen-specific immune populations (NanoString and CyTOF). Two distinct cohorts of 19 and 27 chronic HBV patients, respectively, were analyzed longitudinally prior to and after discontinuation of 2 different NUC therapy strategies.
RESULTS. Absence of hepatic flares following discontinuation of NUC treatment correlated with the presence, during NUC viral suppression, of HBV core and polymerase-specific T cells that were contained within the ex vivo PD-1+ population.
CONCLUSIONS. This study identifies the presence of functional HBV-specific T cells as a candidate immunological biomarker for safe therapy discontinuation in chronic HBV patients. Furthermore, the persistent and functional antiviral activity of PD-1+ HBV–specific T cells highlights the potential beneficial role of the expression of T cell exhaustion markers during human chronic viral infection.
FUNDING. This work was funded by a Singapore Translational Research Investigator Award (NMRC/STaR/013/2012), the Eradication of HBV TCR Program (NMRC/TCR/014-NUHS/2015), the Singapore Immunology Network, the Wellcome Trust (107389/Z/15/Z), and a Barts and The London Charity (723/1795) grant.

StephenW

乙型肝炎病毒特异性T细胞与核苷（酸）类似物治疗中止时的病毒控制相关
Laura Rivino，1 Nina Le Bert，1,2 Upkar S. Gill，1,3 Kamini Kunasegaran，1 Yang Cheng，4 Damien Z.M. Tan，2 Etienne Becht，4 Navjyot K. Hansi，3 Graham R. Foster，3 Suung-Hung Su，5 Tai-Chung Tseng，5 Seng Gee Lim，6 Jia-Horng Kao，5 Evan W. Newell，4 Patrick T.F.肯尼迪，3和安东尼奥·贝托莱蒂1,2,4

首次发布2018年1月8日 - 更多信息

参见解释慢性病毒性肝炎中功能性PD1 + T细胞命运的相关评论。

    抽象

    背景。慢性乙型肝炎病毒（HBV）患者的临床处理完全基于病毒学参数，不能独立地确定哪些患者可以安全地中断核苷（酸）类似物（NUC）疗法。 NUC有效地抑制病毒复制，但不能消除HBV。因此，治疗中断可能与病毒学和生化复发有关，因此，大部分治疗是终生的。

    方法。由于抗病毒免疫是HBV控制的关键，我们通过利用传统免疫学测定（ELISPOT，流式细胞术）连同全球非抗原特异性免疫人群的分析，研究了在慢性HBV患者的免疫谱中安全停止NUC的潜在生物标记（NanoString和CyTOF）。在两种不同的NUC治疗策略停用之前和之后，分别对19名和27名慢性HBV患者的两组不同的队列进行纵向分析。

    结果。停止NUC治疗后没有肝脏闪光与在NUC病毒抑制过程中存在于离体PD-1 +群体内的HBV核心和聚合酶特异性T细胞的存在相关。

    结论。这项研究确定了功能性HBV特异性T细胞的存在，作为慢性HBV患者安全治疗终止的候选免疫生物标志物。此外，PD-1 + HBV特异性T细胞的持续性和功能性抗病毒活性突出了在人慢性病毒感染期间T细胞耗竭标志物表达的潜在有益作用。

    资金。 （NMRC / STaR / 013/2012），根除HBV TCR计划（NMRC / TCR / 014-NUHS / 2015），新加坡免疫学网络，Wellcome Trust（107389 / Z / 15 / Z）以及Barts和伦敦慈善机构（723/1795）。

StephenW

安东尼奥Bertoletti新加坡研究组未料到的研究结果.

https://www.jci.org/articles/view/92812

StephenW

Unravelling the fate of functional PD1+ T cells in chronic viral hepatitis
Eleanor Barnes

First published January 8, 2018 - More info

See the related article at Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation.

Hepatitis B virus (HBV) infection can be managed clinically with nucleos(t)ide therapy, which suppresses viral replication; however, these drugs must often be used long term, as they are unable to fully eliminate the virus. For many patients, discontinuation of treatment results in viral resurgence and hepatic flare, and there is not a reliable way to identify those individuals that can be successfully taken off nucleos(t)ide therapy. In this issue of the JCI, Rivino and colleagues report on their use of a multipronged approach to investigate potential biomarkers indicative of HBV-infected patients who can safely stop nucleos(t)ide therapy. The authors identified a population of HBV-specific, PD1-positive T cells that was present in HBV-infected patients who successfully discontinued treatment without hepatic flare, but not in those that developed flare upon treatment cessation. Together, these results support the concept that PD1+ cells may play an important role in viral control, the further evaluation of this T cell subset in preventing hepatic flare, and the development of assays to better detect this PD1+ T cell population in HBV-infected patients on nucleos(t)ide therapy.

解开慢性病毒性肝炎中功能性PD1 + T细胞的命运
埃莉诺·巴恩斯

首次发布2018年1月8日 - 更多信息

在核苷类似物治疗中止时，参见乙型肝炎病毒特异性T细胞与病毒控制相关的相关文章。

乙型肝炎病毒（HBV）感染可以通过核苷酸（t）治疗临床管理，抑制病毒复制;然而，这些药物往往需要长期使用，因为它们无法完全消除病毒。对于许多患者来说，停止治疗会导致病毒性复发和肝功能不全，而且还没有一种可靠的方法来鉴定那些能够成功脱离核苷（酸）疗法的个体。在本期JCI中，Rivino及其同事报告了他们使用多管齐下的方法来研究潜在的生物标志物，这些生物标志物可以安全地停止核苷（酸）酶治疗。作者确定了HBV特异性PD1阳性T细胞群体，这些T细胞存在于HBV感染的患者中，这些患者成功停止治疗而没有肝脏闪光，但是在治疗结束后没有出现闪光的患者。总之，这些结果支持PD1 +细胞可能在病毒控制中发挥重要作用的概念，进一步评估T细胞亚群在预防肝脏炎症中的作用，以及开发更好地检测HBV感染患者中的PD1 + T细胞群对核苷（酸）治疗。