Stelma Femke, Willemse Sophie B, Erken Robin, de Niet Annikki, Sinnige Marjan J, van Dort Karel, Zaaijer Hans L, van Leeuwen Ester M M, Kootstra Neeltje A, Reesink Hendrik W
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands.
Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.
Open Forum Infect Dis. 2017 Dec 20;4(4):ofx231. doi: 10.1093/ofid/ofx231. eCollection 2017 Fall.
Acute hepatitis B virus infection in adults is generally self-limiting but may lead to chronicity in a minority of patients.
We included 9 patients with acute hepatitis B virus (HBV) infection and collected longitudinal follow-up samples. Natural killer (NK) cell characteristics were analyzed by flowcytometry. HBV-specific T-cell function was analyzed by in vitro stimulation with HBV peptide pools and intracellular cytokine staining.
Median baseline HBV DNA load was 5.12 log IU/mL, and median ALT was 2652 U/mL. Of 9 patients, 8 cleared HBsAg within 6 months whereas 1 patient became chronically infected. Early time points after infection showed increased CD56 NK cells and an increased proportion of cells expressing activation markers. Most of these had normalized at week 24, while the proportion of TRAIL-positive CD56 NK cells remained high in the chronically infected patient. In patients who cleared HBV, functional HBV-specific CD8+ and CD4+ responses could be observed, whereas in the patient who developed chronic infection, only low HBV-specific T-cell responses were observed.
NK cells are activated early in the course of acute HBV infection. Broad and multispecific T-cell responses are observed in patients who clear acute HBV infection, but not in a patient who became chronically infected.
成人急性乙型肝炎病毒感染通常具有自限性,但少数患者可能会发展为慢性感染。
我们纳入了9例急性乙型肝炎病毒(HBV)感染患者,并收集了纵向随访样本。通过流式细胞术分析自然杀伤(NK)细胞特征。通过用HBV肽库进行体外刺激和细胞内细胞因子染色来分析HBV特异性T细胞功能。
基线HBV DNA载量中位数为5.12 log IU/mL,ALT中位数为2652 U/mL。9例患者中,8例在6个月内清除了HBsAg,而1例患者发生了慢性感染。感染后的早期时间点显示CD56 NK细胞增加,表达激活标志物的细胞比例增加。其中大多数在第24周时恢复正常,而在慢性感染患者中,TRAIL阳性CD56 NK细胞的比例仍然很高。在清除HBV的患者中,可以观察到功能性HBV特异性CD8 +和CD4 +反应,而在发生慢性感染的患者中,仅观察到低水平的HBV特异性T细胞反应。
NK细胞在急性HBV感染过程中早期被激活。在清除急性HBV感染的患者中观察到广泛的多特异性T细胞反应,但在发生慢性感染的患者中未观察到。