T淋巴细胞表型对慢性HBV感染免疫状态的影响及应用价值

赵金花; 李俊峰; 毛小荣

doi:10.3969/j.issn.1001-5256.2020.05.014

T淋巴细胞表型对慢性HBV感染免疫状态的影响及应用价值

DOI: 10.3969/j.issn.1001-5256.2020.05.014

1. 兰州大学第一临床医学院
2. 兰州大学第一医院兰州大学第一医院传染病研究室
3. 兰州大学第一医院兰州大学第一医院感染科

基金项目:

国家自然科学基金项目（81800528）；甘肃省卫生行业科研计划项目（GSWSKY2018-24）；兰州大学第一医院院内基金（ldyyyn2017-17）；兰州市城关区科研专项（2018SHFZ0023）；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 959
- HTML全文浏览量: 16
- PDF下载量: 146
- 被引次数: 0
出版历程
- 收稿日期: 2019-12-16
- 出版日期: 2020-05-20

Effect of T-lymphocyte phenotype on immune status in chronic hepatitis B virus infection and its application value

The First Clinical Medical College,Lanzhou University

Research funding:

摘要

摘要:
目的探讨T淋巴细胞表型与慢性乙型肝炎免疫状态的关系及其应用价值。方法纳入2015年1月-2019年5月就诊于兰州大学第一医院的慢性乙型肝炎患者77例,依据HBeAg状态、血清中ALT、HBsAg和HBV DNA水平将其分为免疫耐受期和非免疫耐受期。获取患者T淋巴细胞表型、HBV血清学指标、HBV DNA载量、血常规及肝功能等主要实验室检查指标并计算APRI及FIB-4。符合正态性分布的计量资料2组间比较采用t检验;不符合正态性分布的计量资料2组间比较采用Mann-WhitneyU检验;计数资料组间比较采用χ2检验。两变量间相关效应检验采用Spearman相关分析。采用受试者工作特征曲线下面积（AUC）评价Treg、CD8+PD-1+T淋巴细胞百分比和CD8+CD45RO+T淋巴细胞百分比诊断效能。结果 Treg和CD8+PD-1+百分比在免疫耐受期明显高于非免疫耐受期（U值分别为12. 0、59. 0,P值分别为<0001、0....
- 乙型肝炎,慢性 /
- T淋巴细胞亚群 /
- 免疫,细胞
Abstract:
Objective To investigate the association between T-lymphocyte phenotype and immune status in chronic hepatitis B(CHB)and its application value.Methods A total of 77 CHB patients who attended The First Hospital of Lanzhou University from January 2015 to May 2019 were enrolled, and according to the status of HBeAg and the serum levels of alanine aminotransferase(ALT), HBsAg, and HBV DNA, they were divided into immune tolerance group and non-immune tolerance group. The laboratory results of T-lymphocyte phenotype, HBV serological test, HBV DNA load, routine blood test, and liver function were obtained, and aspartate aminotransferase-to-platelet ratio index(APRI) and fibrosis-4(FIB-4) were calculated. Thettest was used for comparison of normally distributed continuous data between two groups; and the Mann-WhitneyUtest was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. Spearman correlation analysis was used to test the correlation effect between the two variables. The diagnostic efficacy of Treg, CD8+PD-1+T lymphocyte percentage and CD8+CD45 RO+T lymphocyte percentage were evaluated by AUC.Results Compared with the non-immune tolerance group, the immune tolerance group had significantly higher percentages of Treg and CD8+PD-1+T cells(U= 12. 0 and 59. 0,P< 0. 001,P= 0 013) and significantly lower percentages of CD3+CD8+T cells and CD8+CD45 RO+T cells(U= 50. 0 and 38. 5, bothP< 0. 05). Compared with the high HBV DNA load group, the low HBV DNA load group had significantly lower percentages of Treg and CD8+PD-1+T cells(U= 178 5 and 255.0,P= 0. 003 and 0. 018) and significantly higher percentages of CD3+T cells and CD8+CD45 RO+T cells(U= 104. 0 and1495,P= 0. 033 and 0. 025). APRI was negatively correlated with the percentage of Treg(r=-0. 379,P= 0. 013), and FIB-4 was negatively correlated with the percentages of CD3+CD4+, CD3+CD8+, CD4+CD45 RO+, and CD8+CD45 RO+T cells(r=-0. 259,-0. 275,-0. 233, and-0. 229,P= 0. 023, 0. 016, 0. 041, and 0. 045). Treg, CD8+PD-1+T cells, and CD8+CD45 RO+T cellshad an area under the ROC curve of 0. 793(95% confidence interval [CI]: 0. 651-0. 936), 0. 802(95% CI: 0. 678-0. 927), and0. 816(95% CI: 0. 706-0. 927), respectively, in evaluating immune status.Conclusion There are various T-lymphocyte phenotypesin patients with chronic HBV infection, and different T lymphocytes have different abilities to eliminate HBV. Detection of T-lymphocytephenotype helps to understand the immune status and adjust the immune function in CHB patients and can provide a reference for the func-tional cure of CHB patients.
- hepatitis B,chronic /
- T-lymphocyte subsets /
- immunity,cellular

HTML全文

参考文献(16)

[1] GEHRING AJ, PROTZER U. Targeting innate and adaptive immune responses to cure chronic HBV infection[J]. Gastroenterology, 2019, 156(2):325-337.

[2] PROTZER U, MAINI MK, KNOLLE PA. Living in the liver:Hepatic infections[J]. Nat Rev Immunol, 2012, 12(3):201-213.

[3] MUELLER SN, AHMED R. High antigen levels are the cause of T cell exhaustion during chronic viral infection[J]. Proc Natl Acad Sci U S A, 2009, 106(21):8623-8628.

[4] UTZSCHNEIDER DT, ALFEI F, ROELLI P, et al. High antigen levels induce an exhausted phenotype in a chronic infection without impairing T cell expansion and survival[J]. J Exp Med, 2016, 213(9):1819-1834.

[5] KENNEDY P, SANDALOVA E, JO J, et al. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B[J]. Gastroenterology, 2012, 143(3):637-645.

[6] Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2019)[J]. J Clin Hepatol, 2019,35(12):2648-2669.(in Chinese）中华医学会感染病学分会，中华医学会肝病学分会．慢性乙型肝炎防治指南（2019年版）[J]．临床肝胆病杂志，2019, 35(12):2648-2669.

[7] LANG J, NEUMANN-HAEFELIN C, THIMME R. Immunological cure of HBV infection[J]. Hepatol Int, 2019, 13(2):113-124.

[8] RAO PE, PETRONE AL, PONATH PD. Differentiation and expansion of T cells with regulatory function from human peripheral lymphocytes by stimulation in the presence of TGF-{beta}[J]. J Immunol, 2005, 174(3):1446-1455.

[9] WANG X, DONG Q, LI Q, et al. Dysregulated response of follicular helper T cells to hepatitis B surface antigen promotes HBV persistence in mice and associates with outcomes of patients[J]. Gastroenterology, 2018, 154(8):2222-2236.

[10] ASABE S, WIELAND SF, CHATTOPADHYAY PK, et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection[J]. J Virol, 2009, 83(19):9652-9662.

[11] THIMME R, WIELAND S, STEIGER C, et al. CD8(+)T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection[J]. J Virol, 2003, 77(1):68-76.

[12] XIE DY, CHEN FJ, LIN BL, et al. The expressions of PD-1and PD-L1 and the correlation with the degree of liver damage in HBV chronic infection[J/CD]. Chin J Exp Clin Infect Dis(Electronic Version), 2010, 4(3):31-34.(in Chinese）谢冬英，陈凤娟，林炳亮，等．PD-1和PD-L1表达与慢性HBV感染者肝脏病变程度的相关性[J/CD]．中华实验和临床感染病杂志（电子版），2010, 4(3):31-34.

[13] ZHAO HZ, QI QG, LIU RJ, et al. The relationship among programmed death receptor 1 expression of peripheral blood T lymphocytes, hepatitis B virus DNA load and alanine aminotransferase level in chronic hepatitis B patients under different immune status[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2018,12(6):585-589.(in Chinese）赵海珍，其其格，刘瑞军，等．慢性乙型肝炎患者不同免疫状态下外周血T淋巴细胞程序性死亡受体1表达与乙型肝炎病毒DNA载量及丙氨酸氨基转移酶水平的相关性[J/CD]．中华实验和临床感染病杂志（电子版），2018,12(6):585-589.

[14] HOOGEVEEN RC, ROBIDOUX MP, SCHWARZ T, et al. Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection[J].Gut, 2019, 68(5):893-904.

[15] KAH J, KOH S, VOLZ T, et al. Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection[J]. J Clin Invest, 2017, 127(8):3177-3188.

[16] PALEY MA, KROY DC, ODORIZZI PM, et al. Progenitor and terminal subsets of CD8+T cells cooperate to contain chronic viral infection[J]. Science, 2012, 338(6111):1220-1225.

施引文献

资源附件(0)

访问统计