de Groen Rik A, Hou Jun, van Oord Gertine W, Groothuismink Zwier M A, van der Heide Marieke, de Knegt Robert J, Boonstra André
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Antiviral Res. 2017 Apr;140:18-24. doi: 10.1016/j.antiviral.2017.01.007. Epub 2017 Jan 14.
Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection.
Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells.
The overall composition, phenotype, and cytolytic activity of the NK cells remained constant across all clinical phases, with the exception of a few specific markers (KIRs, NKp46). CD56 NK cells of chronic HBV patients differed in their ability to produce IFN-γ between the clinical phases pre- and post-HBeAg seroconversion.
This depicts a shift in NK cell characteristics between the immune active, under heavy viral or immune pressure, and inactive carrier phases, that coincides with HBeAg seroconversion. Although these changes in NK cells do not appear to be completely responsible for differences in liver damage characteristic of specific clinical phases, they could provide a step toward understanding immune dysregulation in chronic HBV infection.
慢性乙型肝炎病毒（HBV）感染可分为4个不同的临床阶段：免疫耐受期、免疫活跃期、非活动携带者期和HBeAg阴性肝炎期。我们最近采用系统生物学方法，确定了先天性免疫反应成分，特别是自然杀伤细胞（NK细胞）是特定HBV临床阶段的一个独特因素。为了扩展这项研究并确定潜在的免疫机制，我们对慢性HBV感染中的NK细胞进行了全面分析。
使用未经治疗的慢性HBV患者的外周血来分析NK细胞的表型标志物、细胞因子产生和细胞毒性。
除了少数特定标志物（杀伤细胞免疫球蛋白样受体、NKp46）外，NK细胞的总体组成、表型和细胞溶解活性在所有临床阶段均保持不变。慢性HBV患者的CD56 NK细胞在HBeAg血清学转换前后的临床阶段之间产生γ干扰素的能力有所不同。
这表明在免疫活跃期（处于重度病毒或免疫压力下）和非活动携带者期之间，NK细胞特征发生了转变，这与HBeAg血清学转换一致。尽管NK细胞的这些变化似乎并不能完全解释特定临床阶段肝脏损伤差异的原因，但它们可能为理解慢性HBV感染中的免疫失调迈出了一步。
