State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.
Department of Laboratory Medicine, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
BMC Immunol. 2023 Nov 25;24(1):47. doi: 10.1186/s12865-023-00579-8.
Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy.
A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses.
In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8 T (P = 0.003), CD4 T (P = 0.033), CD4 T (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4 T (P = 0.010), CD4 T (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients.
Changes in effector CD8 T cells, effector and memory CD4 T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.
肝衰竭主要由乙型肝炎病毒(HBV)引起,可以通过人工肝支持系统(ALSS)得到改善。本研究旨在探讨 ALSS 治疗前后 HBV 相关慢加急性肝衰竭(HBV-ACLF)患者免疫细胞的表型异质性。
共纳入 22 例接受 ALSS 治疗的 HBV-ACLF 患者。根据 ACLF 研究联盟评分,将 ACLF 研究联盟评分 I 级的患者定义为改善。收集并分析患者住院期间的人口统计学和实验室数据。通过液质联用分析检测患者 ALSS 前后外周血的免疫特征。
共有 12 例患者改善,10 例患者未改善。根据 ALSS 后免疫特征数据,未改善患者循环单核细胞比例显著升高,而与改善患者相比,γδT 细胞较少。对 37 个细胞簇进行特征分析表明,ALSS 治疗后,HBV-ACLF 患者效应性 CD8 T(P=0.003)、CD4 T(P=0.033)、CD4 T(P=0.039)和抑制性自然杀伤(NK)细胞(P=0.029)的频率降低。治疗后亚组分析显示,改善患者的 CD4 T(P=0.010)、CD4 T(P=0.021)和 γδT 细胞比例较高,而单核细胞比例较低(P=0.012),与未改善患者相比。
效应性 CD8 T 细胞、效应和记忆 CD4 T 细胞以及抑制性 NK 细胞的变化与 ALSS 治疗 HBV-ACLF 相关。此外,当患者获得不同预后时,单核细胞和 γδT 细胞表现出主要差异。淋巴细胞和单核细胞的表型异质性可能有助于评估 ALSS 预后和未来的免疫治疗策略。