Abd-Elsamie Elham, Kamal-ElDin Taghreed M, Hassaballa Ashraf E, A Medhat, Badawy Eman R, ElMelegy Tarek T, Zahran Asmaa M, Mekky Mohamed A
Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Department of Tropical Medicine & Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Egypt J Immunol. 2019 Jan;26(1):151-161.
Hepatitis C virus (HCV) is a major health problem all over the world with the highest prevalence reported in Egypt. Various treatment regimens have been developed over the last years. Interferon (IFN) based regimen was the standard of care regimen and then the IFN-free therapies were emerged. Host innate immunity through the activity of natural killer (NK) cell is one of the major players in competing infections and tumors, by producing perforin and granzymes that cause cytolysis of target cells, or by the production of various cytokines such as natural interferon gamma. Natural cytotoxicity receptors (NCRs), including Nkp30, Nkp44 and Nkp46, are a group of activating receptors that almost have restricted expression on the surface of NK cells and their density correlates with NK cytotoxicity. The role of these cells is not fully elucidated in patients with chronic HCV infection either treatment-naive or treatment experienced. Therefore, this study aimed to investigate the change that occurs in NK cell activity and cytotoxicity in response to successful elimination of HCV from blood after triple therapy with PEG-IFN-α, ribavirin and sofosbuvir. A total of 56 (50 male: 6 female) HCV patients with mean age of 41.6± 12.1 years were included in this study. They were divided into two groups: treatment naive group (20 patients) and the sustained virologic response (SVR) group (36 patients). All patients were investigated for their NK cell profile, NCRs, perforin and granzyme B expression by flow cytometry. Data was expressed as mean fluorescence intensity (MFI). Results revealed significant increase in MFI of granzyme B (P=0.001) and decrease in MFI of NKp30 (P=0.042) in the SVR group as compared to treatment naïve group. These findings indicated that triple therapy of HCV (IFN, Ribavirin and Sofosbuvir) effected NK activation and cytotoxicity.
丙型肝炎病毒（HCV）是一个全球性的重大健康问题，埃及报告的患病率最高。在过去几年中已经开发出了各种治疗方案。基于干扰素（IFN）的方案曾是标准治疗方案，随后出现了无干扰素疗法。宿主天然免疫通过自然杀伤（NK）细胞的活性发挥作用，是对抗感染和肿瘤的主要参与者之一，它通过产生导致靶细胞溶解的穿孔素和颗粒酶，或通过产生各种细胞因子如天然干扰素γ来实现。天然细胞毒性受体（NCRs），包括Nkp30、Nkp44和Nkp46，是一组激活受体，几乎只在NK细胞表面有受限表达，其密度与NK细胞毒性相关。无论是初治还是经治的慢性HCV感染患者，这些细胞的作用尚未完全阐明。因此，本研究旨在调查聚乙二醇干扰素-α、利巴韦林和索磷布韦三联疗法成功清除血液中的HCV后，NK细胞活性和细胞毒性所发生的变化。本研究共纳入56例（50例男性：6例女性）平均年龄为41.6±12.1岁的HCV患者。他们被分为两组：初治组（20例患者）和持续病毒学应答（SVR）组（36例患者）。通过流式细胞术对所有患者的NK细胞谱、NCRs、穿孔素和颗粒酶B表达进行检测。数据以平均荧光强度（MFI）表示。结果显示，与初治组相比，SVR组颗粒酶B的MFI显著增加（P = 0.001），而NKp30的MFI降低（P = 0.042）。这些发现表明，HCV三联疗法（干扰素、利巴韦林和索磷布韦）影响了NK细胞的激活和细胞毒性。
