HBcAg特异性辅助性T淋巴细胞22在HBV感染者中的变化和意义  

Change and significance of HBcAg-specific Th22 cells in patients with hepatitis B virus infection

作　　者：靳娟 黄小正 靖新艳 张媛 尹金玲 李佳佳 王思思 郭雅玲 李瑛 JIN Juan;HUANG Xiaozheng;JING Xinyan;ZHANG Yuan;YIN Jinling;LI Jiajia;WANG Sisi;GUO Yaling;LI Ying(Department of Antiviral Triage,The Eighth Hospital of Xi’an,Xi’an 710061,China;Department of Medical Affairs,The Eighth Hospital of Xi’an,Xi’an 710061,China;Department of Hepatology,The Eighth Hospital of Xi’an,Xi’an 710061,China)

机构地区：[1]西安市第八医院抗病毒门诊,西安710061 [2]西安市第八医院医务科,西安710061 [3]西安市第八医院肝病科,西安710061

出　　处：《临床肝胆病杂志》2020年第11期2435-2440,共6页Journal of Clinical Hepatology

基　　金：陕西省科技厅科研项目(2020ZDXM-SF-007)。

摘　　要：目的观察HBV感染者中辅助性T淋巴细胞(Th) 22、IL-22和转录因子芳香烃受体(AhR)的变化及与临床指标的相关性。方法选择2018年3月-2019年3月在西安市第八医院就诊的急性乙型肝炎(AHB)患者11例、慢性乙型肝炎(CHB)患者38例和健康对照者(HC) 16例,CHB患者使用替诺福韦酯(TDF)抗病毒治疗,收集AHB患者基线和出院6个月后的外周血,收集CHB患者基线、治疗6个月和治疗12个月的外周血,分离外周血单个核细胞(PBMC)和血浆,分别使用佛波酯+伊乌诺霉素和重组HBcAg刺激PBMC,流式细胞术检测非特异性CD3+CD4+IL-22+的Th22和HBcAg特异性Th22。ELISA检测血浆IL-22水平。实时定量PCR检测PBMC中AhR mRNA水平。符合正态分布的计量资料两组间比较采用t检验、配对t检验,多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验;非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验。计数资料采用χ~2检验。采用Spearman相关性分析进行相关性检验。结果 AHB患者非特异性Th22细胞比例(2.86%±0.45%)高于CHB患者(1.39%±0.33%)和HC(0.80%±0.13%),差异均有统计学意义(t值分别为11.80、17.30,P值均<0.001),CHB患者非特异性Th22细胞比例亦高于HC(t=6.825,P <0.001)。AHB患者HBcAg特异性Th22细胞比例高于CHB患者(2.97%±0.52%vs 1.22%±0.22%,t=16.58,P <0.001)。AHB患者血浆IL-22水平[(130.7±39.97) pg/ml]高于CHB患者[(66.59±20.83) pg/ml]和HC[(50.63±11.07) pg/ml],差异均有统计学意义(t值分别为7.176、7.662,P值均<0.001),CHB患者血浆IL-22水平亦高于HC(t=2.887,P=0.006)。AHB患者PBMC中AhR mRNA(11.45±3.03)高于CHB患者(4.81±1.25)和HC(1.10±0.17),差异均有统计学意义(t值分别为10.85、13.75,P值均<0.001),CHB患者AhR mRNA亦高于HC(t=11.77,P <0.001)。HBcAg特异性Th22细胞比例在AHB患者和CHB患者中均与ALT水平呈显著正相关(r值分别为0.638、0.830,P值分别为0.035、0.002),血浆IL-22水平在AHB患者和CHB患者中亦均ObjectiveTo investigate the changes of Th22 cells,interleukin-22(IL-22),and transcription factor aryl hydrocarbon receptor(AhR)in patients with hepatitis B virus(HBV)infection and their correlation with clinical indices.Methods A total of 11 patients with acute hepatitis B(AHB)and 38 patients with chronic hepatitis B(CHB)who attended Eighth Hospital of Xi’an from March 2018 to March 2019 were enrolled as AHB group and CHB group,respectively,and 16 healthy controls were enrolled as HC group.The patients with CHB received tenofovir disoproxil fumarate(TDF)antiviral therapy.Peripheral blood samples were collected for AHB patients at baseline and 6 months after discharge,and peripheral blood samples were collected for CHB patients at baseline and at months 6 and 12 of treatment;peripheral blood mononuclear cells(PBMCs)and plasma were isolated,then PBMCs were stimulated with phorbol ester+ionomycin or recombinant HBcAg,and flow cytometry was used to measure nonspecific CD3+CD4+IL-22+Th22 cells and HBcAg-specific Th22 cells.ELISA was used to measure the plasma level of IL-22,and quantitative real-time PCR was used to measure the mRNA expression of AhR in PBMCs.The t-test and the paired t-test were used for comparison of normally distributed continuous data between two groups;a one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.The chi-square test was used for comparison of categorical data between groups.A Spearman correlation analysis was used to investigate correlation.Results The AHB group had a significantly higher percentage of nonspecific Th22 cells than the CHB group(2.86%±0.45%vs 1.39%±0.33%,t=11.80,P<0.001)and the HC group(2.86%±0.45%vs 0.80%±0.13%,t=17.30,P<0.001),and the CHB group also had a significantly higher percentage of no

关 键 词：乙型肝炎病毒 乙型肝炎核心抗原 白细胞介素类 TH22细胞 

分 类 号：R512.62[医药卫生—内科学]