Zhou Y Z, Chang Y N, He Y, Wang H M, Peng X R, Chen M, Peng M L, Hu P, Ren H, Xu H M
Department of Infectious Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing 400014, China.
Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Chongqing 400010, China.
Zhonghua Gan Zang Bing Za Zhi. 2021 Sep 20;29(9):837-843. doi: 10.3760/cma.j.cn501113-20210804-00376.
To compare the baseline difference in the quantitative hepatitis B core antibody levels (qAnti-HBc) between non-response and response group in children with HBeAg-positive chronic hepatitis B (CHB) who received antiviral therapy, and further explore the proportion and functional activity of CD8 + memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children. The baseline anti-HBc quantification (qAnti-HBc) levels of 85 children with HBeAg-positive CHB who visited the Department of Infectious Diseases, Children's Hospital of Chongqing Medical University from June 2018 to December 2020 were detected retrospectively. The relationship between the baseline qAnti-HBc level and HBeAg serological response in 37 children who received antiviral therapy was analyzed. The proportion of CD8(+) memory T lymphocyte subsets and the secretion levels of interferon (IFN) γ, and tumor necrosis factor (TNF) α in peripheral blood of 59 children at baseline were detected by flow cytometry. The relationship between qAnti-HBc level and the proportion and functional activity of CD8(+) memory T lymphocyte subsets was analyzed. Pearson's Chi-square test was used to compare the count data. Mann-Whitney U test or Kruskal-Wallis test was used to compare measurement data between two or more groups, and Spearman's rank correlation analysis was used for the correlation between continuous variables. Among 37 children who received entecavir (ETV, 21/37 cases) or pegylated interferon (Peg-IFN, 16/37 cases), 18 cases had developed HBeAg seroconversion (10/ 21 cases in the ETV group, 8/16 cases in the Peg-IFN group). The baseline qAnti-HBc level was significantly higher in the response group [4.71 (4.644.81) log(10)IU/ml] than the non-response group children [4.54 (4.454.64) log(10)IU/ml, = -3.316, = 0.001]. The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes were significantly higher in the high-qAnti-HBc group than the low-qAnti-HBc group ( < 0.05). The proportion of CD8(+) Tem, CD38(+)CD8(+) Tem and CD38(+)CD8(+) Temra cells was significantly higher in ALT > 1× upper limit of normal value (ULN) group than ALT≤1×ULN group ( < 0.05). However, there were no significant differences in the levels of IFNγ and TNFα secreted by CD8(+) T lymphocytes between the two groups ( > 0.05). Spearman's correlation analysis showed that qAnti-HBc was positively correlated with the proportion of CD8(+) Tem, CD38(+)CD8(+) Tem, CD38(+)CD8(+) Temra cells and the level of IFNγ secreted by CD8(+)T lymphocytes ( < 0.05). Additionally, ALT was only positively correlated with the proportion of CD38(+)CD8(+) TEM and CD38(+) CD8(+) Temra cells ( < 0.05). Raised baseline qAnti-HBc level is related to the HBeAg serological response to antiviral therapy in children with CHB. Peripheral blood effector CD8+ T lymphocytes of CHB children with higher qAnti-HBc show stronger phenotype and functional activation characteristics, which may shed some light on the underlying immune mechanism related to antiviral therapy efficacy in children with CHB.
比较接受抗病毒治疗的HBeAg阳性慢性乙型肝炎（CHB）患儿中无应答组与应答组之间乙肝核心抗体定量水平（qAnti-HBc）的基线差异，并进一步探讨不同qAnti-HBC水平患儿外周血中CD8 + 记忆性T淋巴细胞亚群的比例及功能活性。回顾性检测了2018年6月至2020年12月期间就诊于重庆医科大学附属儿童医院感染科的85例HBeAg阳性CHB患儿的基线抗-HBc定量（qAnti-HBc）水平。分析了37例接受抗病毒治疗患儿的基线qAnti-HBc水平与HBeAg血清学应答之间的关系。采用流式细胞术检测了59例患儿基线时外周血中CD8(+)记忆性T淋巴细胞亚群的比例以及干扰素（IFN）γ、肿瘤坏死因子（TNF）α的分泌水平。分析qAnti-HBc水平与CD8(+)记忆性T淋巴细胞亚群的比例及功能活性之间的关系。采用Pearson卡方检验比较计数资料。采用Mann-Whitney U检验或Kruskal-Wallis检验比较两组或多组间的计量资料，采用Spearman秩相关分析分析连续变量之间的相关性。在37例接受恩替卡韦（ETV，21/37例）或聚乙二醇干扰素（Peg-IFN，16/37例）治疗的患儿中，18例发生了HBeAg血清学转换（ETV组10/21例，Peg-IFN组8/16例）。应答组患儿基线qAnti-HBc水平[4.71（4.644.81）log(10)IU/ml]显著高于无应答组患儿[4.54（4.454.64）log(10)IU/ml，Z = -3.316，P = 0.001]。高qAnti-HBc组中CD8(+) Tem、CD38(+)CD(+) Tem、CD38(+)CD8(+) Temra细胞的比例以及CD8(+) T淋巴细胞分泌的IFNγ和TNFα水平均显著高于低qAnti-HBc组（P < 0.05）。ALT > 1×正常上限值（ULN）组中CD8(+) Tem、CD38(+)CD8(+) Tem和CD38(+)CD8(+) Temra细胞的比例显著高于ALT≤1×ULN组（P < 0.05）。然而，两组间CD8(+) T淋巴细胞分泌的IFNγ和TNFα水平无显著差异（P > 0.05）。Spearman相关性分析显示，qAnti-HBc与CD8(+) Tem、CD38(+)CD8(+) Tem、CD38(+)CD8(+) Temra细胞的比例以及CD8(+)T淋巴细胞分泌的IFNγ水平呈正相关（P < 0.05）。此外，ALT仅与CD38(+)CD8(+) TEM和CD38(+) CD8(+) Temra细胞的比例呈正相关（P < 0.05）。CHB患儿基线qAnti-HBc水平升高与抗病毒治疗的HBeAg血清学应答相关。qAnti-HBc较高的CHB患儿外周血效应性CD8 + T淋巴细胞表现出更强的表型和功能激活特征，这可能为CHB患儿抗病毒治疗疗效相关的潜在免疫机制提供一些线索。
