State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Office of Prof. Kangxian Luo, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Interferon Cytokine Res. 2019 Dec;39(12):740-751. doi: 10.1089/jir.2019.0042. Epub 2019 Jul 18.
Treatment of chronic hepatitis B with pegylated-interferon-α-2a (PegIFNα) in pediatric patients can lead to a higher rate of hepatitis B virus (HBV) surface antigen (HBsAg) loss than in adults. However, the mechanism of underlying immune response is not clear. The aim of this study was to explore innate and adaptive immunity, especially HBV-specific T cell responses in hepatitis B e antigen (HBeAg)-positive pediatric patients, who have experienced HBsAg loss. Isolated lymphocytes of 20 HBeAg-positive pediatric patients were collected every 12 weeks until treatment was stopped. The phenotype of T/natural killer (NK) cells and function of HBV-specific T cells were analyzed by flow cytometry. The frequency of CD69 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressed on T cells and TRAIL on CD56 NK cells in patients with HBsAg loss was remarkably higher compared with nonresponse patients. Furthermore, peptide stimulation of HBV-specific T cell responses was increased in patients with HBsAg loss when compared with week 0 and 48, and correlated with decline of viral load. The PegIFNα therapy in pediatric patients triggered T/NK cell activation and HBV-specific T cell responses, thereby contributing to successful viral control.
聚乙二醇干扰素-α-2a(PegIFNα)治疗儿童慢性乙型肝炎可导致乙型肝炎病毒(HBV)表面抗原(HBsAg)丢失率高于成人。然而,其潜在免疫反应的机制尚不清楚。本研究旨在探讨固有和适应性免疫,特别是 HBeAg 阳性的乙型肝炎表面抗原丢失的儿科患者的 HBV 特异性 T 细胞反应。每隔 12 周收集 20 例 HBeAg 阳性儿科患者的分离淋巴细胞,直至治疗停止。通过流式细胞术分析 T/自然杀伤(NK)细胞的表型和 HBV 特异性 T 细胞的功能。与无应答患者相比,HBsAg 丢失患者的 T 细胞和 CD56 NK 细胞上 CD69 和肿瘤坏死因子相关凋亡诱导配体(TRAIL)的表达以及 TRAIL 的频率显著升高。此外,与 0 周和 48 周相比,HBsAg 丢失患者的 HBV 特异性 T 细胞反应的肽刺激增加,并且与病毒载量下降相关。PegIFNα 治疗儿科患者可触发 T/NK 细胞激活和 HBV 特异性 T 细胞反应,从而有助于成功控制病毒。