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

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

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-Whitney U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<0.001、0.013),CD3+CD8+百分比和CD8+CD45RO+百分比在免疫耐受期均显著低于非免疫耐受期(U值分别为50.0、38.5,P值均<0.05);Treg和CD8+PD-1+百分比在HBV DNA低载量组明显低于HBV DNA高载量组,差异有统计学意义(U值分别为178.5、255.0,P值分别为0.003、0.018);CD3+百分比和CD8+CD45RO+百分比在HBV DNA低载量组明显高于HBV DNA高载量组,差异有统计学意义(U值分别为104.0、149.5,P值分别为0.033、0.025)。APRI与Treg百分比呈负相关(r=-0.379、P=0.013),FIB-4与CD3+CD4+、CD3+CD8+、CD4+CD45RO+、CD8+CD45RO+百分比与呈负相关(r值分别为-0.259、-0.275、-0.233、-0.229,P值分别为0.023、0.016、0.041、0.045)。Treg、CD8+PD-1+及CD8+CD45RO+百分比对免疫状态的评估效能曲线下面积分别为0.793(95%CI∶0.651~0.936)、0.802(95%CI∶0.678~0.927)和0.816(95%CI∶0.706~0.927)。结论在慢性HBV感染者中存在T淋巴细胞表型的紊乱,不同的T淋巴细胞对HBV的清除作用不同。检测T淋巴细胞表型有助于了解患者免疫状态及调整免疫功能,为达到慢性乙型肝炎患者的功能性治愈提供依据。

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.The t test was used for comparison of normally distributed continuous data between two groups;and the Mann-Whitney U test 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+CD45RO+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+CD45RO+T cells(U=50.0 and 38.5,both P<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+CD45RO+T cells(U=104.0 and 149.5,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+CD45RO+,and CD8+CD45RO+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+CD45RO+T cells had 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),and 0.816(95%CI:0.706-0.927),respectively,in evaluating immune status.Conclusion There are various T-lymphocyte phenotypes in patients with chronic HBV infection,and different T lymphocytes have different abilities to eliminate HBV.Detection of T-lymphocyte phenotype helps to understand the immune status and adjust the immune function in CHB patients and can provide a reference for the functional cure of CHB patients.