在慢性乙型肝炎的聚乙二醇化干扰素α-2b治疗期间，NKp30 + NK

StephenW

NKp30+ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B

    Xiaokun Shen, Binqing Fu, Yanyan Liu, Chuang Guo, Ying Ye, Rui Sun, Jiabin Li, Zhigang Tian & Haiming Wei

    Scientific Reports 6, Article number: 38778 (2016)
    doi:10.1038/srep38778
   

Abstract

A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-α) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-α is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30+ natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. The responders and non-responders differed in the frequency of polyfunctional IFN-γ+ CD107+ NK cells. In addition, the increase in NKp30+ NK cells was negatively correlated with the HBV viral load and plasma HBeAg. Moreover, it was found that IL-15 may contribute to the up-regulation of NKp30 on the NK cells, and this up-regulation was not induced in vitro by Peg-IFN-α-2b alone. However, in the non-responders, these NKp30+ NK cells were dysfunctional because of increased NKG2A expression, which partly explains the inactivation of NKp30+ NK cells and the reduced capacity of these cells to produce antiviral cytokines. These findings may provide a new mechanism to explain the variable efficacy of Peg-IFN-α-2b therapy.

StephenW

在慢性乙型肝炎的聚乙二醇化干扰素α-2b治疗期间，NKp30 + NK细胞与HBV对照相关

    沉小军，沉清庆，刘燕燕，郭国国，叶烨，孙瑞，李家宾，志志刚，海明伟

    科学报告6，产品编号：38778（2016）
    doi：10.1038 / srep38778
   

抽象

迫切需要改善慢性乙型肝炎（CHB）的治疗选择。聚乙二醇化干扰素-α（Peg-IFN-α）在许多情况下实现持续的脱离治疗反应，因为其直接的抗病毒作用和免疫反应的调节。然而，对Peg-IFN-α的无反应性是频繁的，并且机制不甚了解。在这项研究中，我们发现在Peg-IFN-α-2b单一治疗或与阿德福韦酯联合治疗患者中，NKp30 +天然杀伤（NK）细胞的频率和绝对数目显着增加，伴随着增强的CD107a和IFN-与CHB，特别是在应答者。应答者和无应答者在多功能IFN-γ+ CD107 + NK细胞的频率上不同。此外，NKp30 + NK细胞的增加与HBV病毒载量和血浆HBeAg呈负相关。此外，发现IL-15可能有助于NK细胞上的NKp30的上调，并且这种上调不是通过单独的Peg-IFN-α-2b在体外诱导的。然而，在无反应者中，这些NKp30 + NK细胞功能障碍，因为增加NKG2A表达，这部分解释了NKp30 + NK细胞的失活和这些细胞产生抗病毒细胞因子的能力降低。这些发现可能提供一种新的机制来解释Peg干扰素-α2b治疗的可变功效。

StephenW

http://www.nature.com/articles/s ... Id=MTA2MjYxNjU1MwS2