qAnti-HBc与慢性乙型肝炎儿童抗病毒疗效的相关性分析及可能免疫机制探索  

Correlation of qAnti-HBc with antiviral efficacy in children with chronic hepatitis B and exploration of its possible immune mechanism

作　　者：周英芝 常宇南 何怡 王慧敏 彭小蓉[1] 陈敏[2] 彭明利[2] 胡鹏[2] 任红[2] 许红梅[1] Zhou Yingzhi;Chang Yunan;He Ti;Wang Huimin;Peng Xiaorong;Chen Min;Peng Mingli;Hu Peng;Ren Hong;Xu Hongmei(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 In fectious Diseases,the Second A ffiliated Hospital of Chongqing Medical University,Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education),Institute for Viral Hepatitis,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属儿童医院感染科,国家儿童健康与疾病临床医学研究中心,儿童发育疾病研究教育部重点实验室,儿童感染免疫重庆市重点实验室,400014 [2]重庆医科大学附属第二医院感染科,教育部感染性疾病分子生物学重点实验室,重庆医科大学病毒性肝炎研究所,400010

出　　处：《中华肝脏病杂志》2021年第9期837-843,共7页Chinese Journal of Hepatology

基　　金：十三五国家科技项目重大专项(20172X10202203007008)。

摘　　要：目的﹑比较行抗病毒治疗的HBeAg阳性慢性乙型肝炎(CHB)患儿无应答组和应答组间基线乙型肝炎核心抗体定量(qAnti-HBc)水平的差异,以探讨不同qAnti-HBc水平患儿外周血CD_(8)^(+)记忆T细胞亚群比例及其功能活性。方法︰回顾性检测2018年6月至2020年12月于重庆医科大学附属儿童医院感染科就诊的85例HBeAg阳性CHB患儿基线qAnti-HBc水平。分析其中37例抗病毒治疗患儿基线qAnti-HBc水平与HBeAg血清学应答的关系。流式细胞检测59例患儿基线外周血CD_(8)^(+)记忆T细胞亚群比例及干扰素(IFN)-γ、肿瘤坏死因子(TNF)-α分泌水平,分析qAnti-HBc水平与CD_(8)^(+)记忆T细胞亚群比例及其功能活性间的关系。计数资料比较采用Pearson's Chi-square检验,两组或多组间计量资料比较采用Mann-Whitney U检验或Kruskal-Wallis检验,连续性变量间的相关性采用Spearman秩相关分析。结果﹐在37例接受恩替卡韦(ETV,21/37)或聚乙二醇干扰素)(Peg-IFN,16/37)治疗的患儿中,有18例发生HBeAg血清学转换(ETV组10/21,Peg-IFN组8/16),应答组患儿基线qAnti-HBc水平[4.71(4.64~4.81)log_(10)IU/ml]显著高于无应答组[4.54(4.45~4.64)log_(10)IU/ml,Z=-3.316,P=0.001]。高qAnti-HBc组CD8^(+)Tem,CD38^(+)CD8^(+)Tem、CD38^(+)CD8^(+)Temra细胞比例及CD8^(+)T细胞分泌的IFN-γ、TNF-α水平显著高于低qAnti-HBc组(P<0.05);ALT>1×正常值上限(ULN)组CD8^(+)Tem、CD38^(+)CD8^(+)Tem,CD38^(+)CD8^(+)Temra细胞比例显著高于ALT≤1×ULN组(P<0.05),但两组CD8T细胞分泌的IFN-γ、TNF-α水平差异无统计学意义(P>0.05)。Spearman相关分析显示,qAnti-HBc与CD8^(+)Tem、CD38^(+)CD8^(+)Tem、CD38^(+)CD8^(+)Temra细胞比例及CD8^(+)T细胞分泌的IFN-γ水平呈正相关(P<0.05),ALT仅与CD38^(+)CD8^(+)Tem、CD38^(+)CD8^(+)Temra细胞比例呈正相关(P<0.05)。结论﹑较高的基线qAnti-HBc水平与CHB儿童患者抗病毒治疗HBeAg血清学应答相关﹔qAnti-HBc较高的CHB患儿外周血效应CD8T细胞表现出更�Objective To compare the baseline difference in the quantitative hepatitis B core antibody levels(qAnti-HBc)between non-response and response group in children with HBcAg-positive chronic hepatitis B(CHB)who received antiviral therapy,and further explore the proportion and flinctional activity of CDS+memory T lymphocyte subsets with different qAnti-HBC levels in peripheral blood of children.Methods The baseline anti-FI Be 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.Results 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(4.64〜4.81)log10IU/ml]than the non-response group children[4.54(4.45〜4.64)log10IU/ml,Z=-3.316,P=0.001].The proportion of CD8 Tem,CD38^(+)TD8 ^(+)Tem,CD38^(+)CD^(+)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(P<0.05).Th

关 键 词：慢性乙型肝炎 乙型肝炎核心抗体定量 CD8阳性T细胞 儿童 

分 类 号：R725.1[医药卫生—儿科]