外周血淋巴细胞亚群在慢性HBV感染过程中表达的变化分析

翁奉武; 郭丽颖; 李秋伟; 李力; 赵立聪; 孙小雪; 尹美君; 贾建伟

doi:10.3969/j.issn.1001-5256.2020.01.015

外周血淋巴细胞亚群在慢性HBV感染过程中表达的变化分析

DOI: 10.3969/j.issn.1001-5256.2020.01.015

1. 天津中医药大学研究生学院
2. 天津市第二人民医院中医中西医结合Ⅰ科

基金项目:

“十三五”国家科技重大专项(2018ZX10725506-002)；国家中医药防治传染病重点研究室建设项目(国中医药函〔2010〕34号)；

详细信息

中图分类号: R512.62;R575.2
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出版历程
- 收稿日期: 2019-08-16
- 出版日期: 2020-01-20

Change in the expression of peripheral blood lymphocyte subsets during disease progression in patients with chronic hepatitis B virus infection

Graduate School of Tianjin University of Traditional Chinese Medicine

Research funding:

摘要

摘要: 目的探讨HBV感染患者外周血淋巴细胞亚群在疾病进展过程中的表达变化。方法选取2018年1月-2019年4月在天津市第二人民医院住院的慢性HBV感染患者共132例,其中慢性乙型肝炎患者47例,乙型肝炎肝硬化患者44例,乙型肝炎肝硬化相关原发性肝癌患者41例。另选取同期健康体检者42例作为对照组。采用流式细胞术检测4组外周血淋巴细胞亚群精准计数,比较4组外周血淋巴细胞亚群的表达水平。正态分布的计量资料,组间方差不齐采用Welch方差分析,两两比较采用GamesHowell检验。非正态分布的计量资料多组间及进一步两两比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。相关性分析采用Spearman检验。结果与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD3+、CD4+T淋巴细胞数量明显减少,差异均有统计学意义（P值均<0. 05）。与对照组相比,肝癌组CD8+T淋巴细胞数量明显减少,差异有统计学意义（P <0. 05）;与慢性乙型肝炎组相比,肝硬化组和肝癌组CD8+T淋巴细胞数量明显减少,差异均有统计学意义（P值均<0. 05）。与对照组和慢性乙型...
- 乙型肝炎,慢性 /
- 肝硬化 /
- 肝肿瘤 /
- T淋巴细胞 /
- B淋巴细胞 /
- 自然杀伤T细胞
Abstract: Objective To investigate the change in the expression of peripheral blood lymphocyte subsets during disease progression in patients with chronic hepatitis B virus(HBV) infection. Methods A total of 132 patients with chronic HBV infection who were hospitalized in Tianjin Second People's Hospital from January 2018 to April 2019 were enrolled,and among these patients,47 had chronic hepatitis B,44 had hepatitis B cirrhosis(cirrhosis group),and 41 had hepatitis B cirrhosis-related primary liver cancer(liver cancer group). A total of 42 healthy individuals who underwent physical examination during the same period of time were enrolled as control group. Flow cytometry was used to measure the accurate counts of peripheral blood lymphocyte subsets,and the expression of peripheral blood lymphocyte subsets was compared between the four groups. A Welch analysis of variance was used for comparison of normally distributed continuous data with heterogeneity of variance between groups,and the Games-Howell 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 groups. The chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to investigate correlation. Results Compared with the control group and the chronic hepatitis B group,the cirrhosis group and the liver cancer group had significant reductions in the numbers of CD3+and CD4+T cells(all P < 0. 05). Compared with the control group,the liver cancer group had a significant reduction in the number of CD8+T cells(P < 0. 05); compared with the chronic hepatitis B group,the cirrhosis group and the liver cancer group had a significant reduction in the number of CD8+T cells(both P < 0. 05). Compared with the control group and the chronic hepatitis B group,the cirrhosis group and the liver cancer group had a significant reduction in the number of CD19+B cells(all P < 0. 05). Compared with the control group,the cirrhosis group and the liver cancer group had a significant reduction in the number of CD16+CD56+natural killer(NK) cells(both P < 0. 05); compared with the chronic hepatitis B group,the liver cancer group had a significant reduction in the number of CD16+CD56+NK cells(P < 0. 05). In the four groups,disease progression was negatively correlated with peripheral blood CD3+T cells,CD4+T cells,CD8+T cells,CD19+B cells,and CD16+CD56+NK cells(r =-0. 414,-0. 503,-0. 269,-0. 435,and-0. 402,all P < 0. 01).Conclusion In patients with chronic HBV infection,immune status changes with disease progression. Accurate counting of peripheral blood lymphocyte subsets can reflect the immune status of the body and can thus be used as a reference for evaluating clinical evolution,treatment outcome,and prognosis of chronic HBV infection.
- hepatitis B,chronic /
- liver cirrhosis /
- liver neoplasms /
- T-lymphocytes /
- B-lymphocytes /
- natural killer T-cells

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参考文献(21)

[1] BONI C,BARILI V,ACERBI G,et al. HBV immune-therapy:From molecular mechanisms to clinical applications[J]. Int J Mol Sci,2019,20(11):2754.

[2] TANG J,WU ZY,DAI RJ,et al. Hepatitis B virus-persistent infection and innate immunity defect:Cell-related or virusrelated?[J]. World J Clin Cases,2018,6(9):233-241.

[3] RUAN B,YU Z,YANG S,et al. Establishment and development of national community-based collaborative innovation demonstration areas to achieve the control target of hepatitis B in China[J]. BMC Infect Dis,2019,19(1):617.

[4] BERTOLETTI A,KENNEDY P. HBV antiviral immunity:Not all CD8 T cells are born equal[J]. Gut,2019,68(5):770-773.

[5] Chinese Society of Infetious Disease,Chinese Society of Hepatology,Chinese Medical Association. The expert consensus on functional cure of chronic hepatitis B[J]. J Clin Hepatol,2019,35(8):1693-1701.(in Chinese)中华医学会感染病学分会，中华医学会肝病学分会．慢性乙型肝炎临床治愈(功能性治愈)专家共识[J]．临床肝胆病杂志，2019,35(8):1693-1701.

[6] Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会，中华医学会感染病学分会．慢性乙型肝炎防治指南(2015年更新版)[J]．临床肝胆病杂志，2015,31(12):1941-1960.

[7] National Health and Family Planning Commission of the People’s Republic of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会．原发性肝癌诊疗规范(2017年版)[J]．临床肝胆病杂志，2017,33(8):1419-1431.

[8] SUSLOV A,WIELAND S,MENNE S. Modulators of innate immunity as novel therapeutics for treatment of chronic hepatitis B[J]. Curr Opin Virol,2018,30:9-17.

[9] YANG Y,HAN Q,ZHANG C,et al. Hepatitis B virus antigens impair NK cell function[J]. Int Immunopharmacol,2016,38:291-297.

[10] SALIMZADEH L,LE BERT N,DUTERTRE CA,et al. PD-1blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection[J]. J Clin Invest,2018,128(10):4573-4587.

[11] MIAO J,YUAN CY,LI QW,et al. An analysis on correlations between expressions of CD4+and CD8+T lymphocytes in peripheral blood and quantitative level of HBsAg in patients with chronic hepatitis B virus infection[J]. Chin J TCM WM Crit Care,2016,23(4):399-403.(in Chinese)苗静，袁晨翼，李秋伟，等．慢性乙型肝炎病毒感染患者外周血CD4+、CD8+T细胞的表达与HBsAg定量的相关性分析[J]．中国中西医结合急救杂志，2016,23(4):399-403.

[12] RIAZALHOSSEINI B,MOHAMED Z,APALASAMY YD,et al.Association between microRNA-196A2 and microRNA-146A polymorphisms and progression to cirrhosis and hepatocellular carcinoma in patients with viral hepatitis B[J]. Pharmacogenet Genomics,2016,26(2):74-79.

[13] LI CD,CHEN XL,DUAN ZJ,et al. Determination of proportions of T cell subsets and levels of interleukin-15 and interleukin-16 in peripheral blood of patients with chronic hepatitis B virus infection and correlation between them[J]. J Clin Hepatol,2015,31(11):1857-1861.(in Chinese)李彩东，陈锡莲，段正军，等．慢性HBV感染者外周血T淋巴细胞亚群的变化及其与白细胞介素15、白细胞介素16的相关性分析[J]．临床肝胆病杂志，2015,31(11):1857-1861.

[14] SUN KK,HUANG CH,WANG YY,et al. Detection of T lymphocyte surface costimulatory molecules and T lymphocyte subsets in peripheral blood of HBV infected patients and its clinical significance[J]. Chin J Clin Pharmacol Ther,2019,24(3):241-247.(in Chinese)孙凯凯，黄春红，王云云，等．HBV感染者外周血T淋巴细胞表面共刺激分子和T淋巴细胞亚群的检测及临床意义[J]．中国临床药理学与治疗学，2019,24(3):241-247.

[15] CORTI D,LANZAVECCHIA A. Broadly neutralizing antiviral antibodies[J]. Annu Rev Immunol,2013,31(1):705-742.

[16] PEPPA D,GILL US,REYNOLDS G,et al. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cellmediated deletion[J]. J Exp Med,2013,210(1):99-114.

[17] LIU EH,LIU CM. Quantitative changes of peripheral blood lymphocyte subsets and HBV DNA in patients with chronic HBV infection under different pathological conditions[J]. J Baotou Med Coll,2018,34(10):13-15.(in Chinese)刘恩惠，刘传苗．慢性HBV感染者不同病理状态下外周血淋巴细胞亚群及HBV DNA定量变化[J]．包头医学院学报，2018,34(10):13-15.

[18] LIU X,HE L,HAN J,et al. Association of neutrophil-lymphocyte ratio and T lymphocytes with the pathogenesis and progression of HBV-associated primary liver cancer[J]. PLo S One,2017,12(2):e0170605.

[19] WANG Y,HUANG YY,MA Y,et al. Expression features of follicular helper T cells in peripheral blood in patients with chronic hepatitis B[J]. J Clin Hepatol,2018,34(1):58-62.(in Chinese)王燕，黄友英，马燕，等．慢性乙型肝炎患者外周血中滤泡辅助性T淋巴细胞的表达特征[J]．临床肝胆病杂志，2018,34(1):58-62.

[20] YANG C,LI N,WANG Y,et al. Serum levels of B-cell activating factor in chronic hepatitis B virus infection:Association with clinical diseases[J]. J Interferon Cytokine Res,2014,34(10):787-794.

[21] SHI J,ZHAO J,ZHANG X,et al. Activated hepatic stellate cells impair NK cell anti-fibrosis capacity through a TGF-β-dependent emperipolesis in HBV cirrhotic patients[J]. Sci Rep,2017,7:44544.

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