Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Int Immunopharmacol. 2018 Sep;62:59-66. doi: 10.1016/j.intimp.2018.06.043. Epub 2018 Jul 5.
Much evidence indicates that the soluble antigens secreted by hepatitis B virus (HBV) inhibit the function of the immune system. The aim of this study is to investigate, after treatment with nucleoside (acid) analogs (NAs) and the inhibition of viral replication, whether the immune systems of patients with a peripheral blood HBV-DNA level <1000 IU/mL, hepatitis B e antigen (HBeAg) disappearance, and a decrease in hepatitis B surface antigen (HBsAg) levels could be reconstructed.
The frequency and phenotype of circulating natural killer (NK) cells, dendritic cells (DCs), T-helper (Th) cells, regulatory T (Treg) cells, CD4, CD8 T cells, T follicular helper (Tfh) cells and B cells subtypes were tested by flow cytometry in chronic hepatitis B (CHB) patients and healthy controls (HCs). The levels of HBV-related serum HBsAg, HBeAg, HBV-DNA load, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined.
Regarding the innate immune system, an increased frequency of CD56 NK cells was found in the therapeutic response (TR) group compared with that in the immune-active phase (IA) group. Additionally, regarding the adaptive immune system, the Th17/CD4CD25CD127Treg ratio was reduced in the TR group. Additionally, the frequency of CD40LCXCR5CD4T cells and CD40CD19CD27CD38B cells was significantly higher than that of HCs, while that of PDL1CD19 B cells was lower. Furthermore, the frequencies of CTLA4CD4T cells and CTLA4CD8T cells in patients with CHB were significantly higher than those in HCs.
After NA treatment and the inhibition of viral replication, circulating CD56 NK cells and the balance of Th17/Treg can be recovered. Restoring circulating CD56 NK cells and the Th17/Treg balance may help reduce HBsAg levels in patients.
大量证据表明，乙型肝炎病毒（HBV）分泌的可溶性抗原抑制免疫系统的功能。本研究旨在探讨经核苷（酸）类似物（NAs）治疗和病毒复制抑制后，外周血 HBV-DNA<1000IU/mL、乙型肝炎 e 抗原（HBeAg）消失和乙型肝炎表面抗原（HBsAg）水平降低的患者的免疫系统是否能够重建。
采用流式细胞术检测慢性乙型肝炎（CHB）患者和健康对照（HC）外周血自然杀伤（NK）细胞、树突状细胞（DC）、辅助性 T 细胞（Th）、调节性 T（Treg）细胞、CD4、CD8T 细胞、滤泡辅助性 T（Tfh）细胞和 B 细胞亚群的频率和表型。检测 HBV 相关血清 HBsAg、HBeAg、HBV-DNA 载量、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平。
在治疗应答（TR）组中，与免疫活性期（IA）组相比，CD56NK 细胞的频率增加。此外，在适应性免疫方面，TR 组 Th17/CD4CD25CD127Treg 比值降低。此外，CD40LCXCR5CD4T 细胞和 CD40CD19CD27CD38B 细胞的频率明显高于 HC，而 PDL1CD19B 细胞的频率较低。此外，CHB 患者 CTLA4CD4T 细胞和 CTLA4CD8T 细胞的频率明显高于 HC。
NA 治疗和病毒复制抑制后，循环 CD56NK 细胞和 Th17/Treg 平衡可以恢复。恢复循环 CD56NK 细胞和 Th17/Treg 平衡可能有助于降低患者的 HBsAg 水平。
