慢性乙型肝炎病毒（HBV）感染自然杀伤细胞特征是伴有乙肝

StephenW

Natural Killer Cell Characteristics in Patients With Chronic Hepatitis B Virus (HBV) Infection Are Associated With HBV Surface Antigen Clearance After Combination Treatment With Pegylated Interferon Alfa-2a and Adefovir

    Femke Stelma1,2, Annikki de Niet1,2, Marjan J. Tempelmans Plat-Sinnige2, Louis Jansen1,2, R. Bart Takkenberg1, Hendrik W. Reesink1,2, Neeltje A. Kootstra2 and Ester M. M. van Leeuwen2

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Author Affiliations

    1Department of Gastroenterology and Hepatology
    2Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands

    Correspondence: Hendrik W. Reesink, MD, PhD, Academic Medical Center, Department Gastroenterology and Hepatology, Rm G4-215, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands ([email protected]).

    Presented in part: Annual Meeting of the Dutch Society for Immunology, 17–19 December 2014, Kaatsheuvel, The Netherlands. Abstract 79.

Abstract

Background. The role of natural killer (NK) cells in the process of hepatitis B virus (HBV) surface antigen (HBsAg) clearance and whether their phenotype is related to treatment outcome in patients with chronic hepatitis B are currently unknown.

Methods. Patients with chronic hepatitis B (HBV DNA load, >17 000 IU/mL) were treated with pegylated interferon alfa-2a and adefovir for 48 weeks. NK cell phenotype and function were analyzed in 7 responders (defined as individuals with HBsAg clearance by week 72; 3 HBV e antigen [HBeAg]-positive and 4 HBeAg-negative), 7 matched nonresponders, and 7 healthy controls. Subsequently, 34 baseline samples from HBeAg-positive patients with chronic hepatitis B were analyzed.

Results. During treatment, the percentage and absolute number of CD56bright NK cells increased significantly, whereas the percentage and absolute number of CD56dim NK cells decreased. At baseline, responders had a significantly lower expression of chemokine receptor CX3CR1 on CD56bright NK cells and inhibitory receptor NKG2A on CD56dim NK cells, compared with nonresponders. In addition, responders had higher CD56bright TRAIL expression and interferon γ production at end of treatment. These baseline differences were not found in HBeAg-positive patients who had HBeAg seroconversion without HBsAg clearance.

Conclusions. Combination therapy significantly influences NK cell phenotype and function. Differences between patients with chronic hepatitis B with HBsAg clearance and nonresponders suggest that NK cells play a role in the clearance of HBsAg during interferon-based combination therapy.

StephenW

慢性乙型肝炎病毒（HBV）感染自然杀伤细胞特征是伴有乙肝病毒表面抗原的清除结合治疗聚乙二醇干扰素α-2a和阿德福韦后

    Femke Stelma1,2，Annikki德Niet1,2，马里安J. Tempelmans开发平台，Sinnige2，路易斯Jansen1,2，R.巴特Takkenberg1，亨德里克·W·Reesink1,2，去往Neeltje A. Kootstra2酯MM面包车Leeuwen2

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作者机构

    胃肠病学和肝病学教研室
    2Experimental免疫学，医学学术中心，阿姆斯特丹，荷兰

    函授：亨德里克W. Reesink，医学博士，学术医疗中心，消化内科和肝病，RM G4-215，Meibergdreef 9，1105 AZ阿姆斯特丹，荷兰（[email protected]）。

    呈现在部分：荷兰学会年会免疫学，12月17-19日2014年，Kaatsheuvel的，荷兰。摘要79。

抽象的

背景。自然杀伤（NK）细胞在乙型肝炎病毒（HBV）表面抗原（HBsAg）的间隙的过程中，以及是否他们的表型是在慢性乙型肝炎有关治疗结果的作用目前尚不清楚。

方法。有慢性乙型肝炎（HBV DNA载量> 17 000 IU / mL）的患者采用聚乙二醇干扰素α-2a和阿德福韦48周。 NK细胞的表型和功能的7反应进行了分析（定义为HBsAg清除由72周个人; 3乙肝病毒e抗原[大三阳]阳性和4 HBeAg阴性），7匹配无反应者和7名健康对照。随后，来自HBeAg阳性慢性乙型肝炎34基准样品进行了分析。

结果。在治疗期间，百分比和CD56bright NK细胞的绝对数量显著增加，而CD56dim NK细胞的百分比和绝对数量减少。基线时，应答者的趋化因子受体CX3CR1对CD56bright NK细胞和CD56dim NK细胞抑制性受体NKG2A一个显著低表达，与无应答者相比。此外，应答者更高CD56bright TRAIL表达和干扰素γ的产生在治疗结束。在HBeAg阳性患者谁了HBeAg血清学转换无HBsAg清除，未发现这些基线的差异。

结论。组合疗法显著影响NK细胞表型和功能。患者与乙肝表面抗原清除率和无应答慢性乙型肝炎之间的差异表明，NK​​细胞在乙肝表面抗原在干扰素为基础的联合疗法的清除作用。