慢性乙型肝炎患者抗病毒治疗循环血中sPD-1/sPD-L1与T淋巴细胞亚群相关性分析

目的检测慢性乙型肝炎CHB患者循环血可溶性程序性死亡因子sPD-1/可溶性程序性死亡因子配体-1sPD-L1的水平表达,了解抗乙肝病毒治疗对CHB患者循环血sPD-1/sPD-L1表达水平的影响,分析sPD-1/sPD-L1与ALT、AST、HBV DNA水平间的相关性,探讨sPD-1/sPD-L1水平与CHB患者循环血T淋巴细胞亚群间的关系。方法采用酶联免疫法检测各观察时点的sPD-1/sPD-L1水平表达,运用实时荧光定量PCR法检测HBV-DNA载量,采用化学发光法检测乙肝病毒感染标志物,及运用全自动生化分析仪测定肝功能指标。结果治疗前CHB患者循环血sPD-1、sPD-L1表达水平,较健康体检者组及HBV携带者组高表达（P<0.01）;随着抗乙肝病毒治疗时间的延长,其表达水平逐渐下降,在抗乙肝病毒治疗第24周时循环血sPD-1、sPD-L1表达水平较治疗前显著下调（P<0.01）,较健康体检者组、HBV携带者组比较差异无统计学意义（P>0.05）。治疗前CHB患者ALT、AST、TBIL表达水平及HBV DNA载量与sPD-L1水平间呈正相关;治疗24周后CHB患者循环血中ALT、AST、TBIL表达水平、HBV DNA载量与sPD-1/sPD-L1水平间均无相关性。治疗前CHB患者循环血sPD-1与CD3+T与CD4+T、CD8+T淋巴细胞亚群水平正相关;治疗24周后CHB患者循环血中sPD-1、sPD-L1水平与CD3+T、CD4+T、CD8+T淋巴细胞亚群水平间均无相关性。结论抗病毒治疗能抑制HBV DNA复制并调节CHB患者循环血中sPD-1、sPD-L1及T淋巴细胞各亚群水平表达,可在一定程度上反应肝组织损伤程度和HBV的复制水平。

Analysis of Correlation Between sPD-1/sPD-L1 in Circulating Blood and T Lymphocyte Subsets in Patients with Chronic Hepatitis B Treated with Antiviral Therapy.

Objective To detect the level of sPD-1/sPD-L1 in the circulating blood of patients with chronic hepatitis B(CHB), understand the effect of antiviral therapy on the expression level of sPD-1/sPD-L1 in the peripheral blood of patients with CHB, and analyze the correlation between sPD-1/sPD-L1 with ALT, AST and HBV DNA levels. Explore the relationship between sPD-1/sPD-L1 level and peripheral blood T lymphocyte subsets in CHB patients.Methods The levels of sPD-1/sPD-L1 at each observation point were detected by ELISA, HBV-DNA load was detected by real-time quantitative PCR, hepatitis B virus infection markers were detected by chemiluminescence, and liver function indicators were detected by automatic biochemical analyzer.Results Before treatment, the expression levels of sPD-1/sPD-L1 in peripheral blood of CHB patients were significantly higher than that of the healthy checkup group and the HBV carrier group(P<0.01).The expression levels of sPD-1/sPD-L1 in peripheral blood of the treatment group were significantly decreased at the 24th week of antiviral treatment, with statistically significant difference compared with that before treatment(P<0.01), while there was no statistically significant difference between the healthy checkup group and the HBV carrier group(P<0.05).Before treatment, the expression levels of ALT, AST and TBIL in CHB patients and HBV DNA load were positively correlated with the level of sPD-L1 .There was no correlation between ALT,AST,TBIL expression level, HBV DNA load and sPD-1 level.After 24 weeks of treatment, there was no correlation between ALT, AST, TBIL, HBV DNA load and sPD-1/sPD-L1 levels in CHB patients peripheral blood.sPD-1 and CD3+T were positively correlated with CD4+T and CD8+T lymphocyte subsets in CHB patients before treatment;There was no correlation between sPD-1/sPD-L1 expression.There was no significant correlation between sPD-L1 and CD3+T, CD4+T and CD8+T lymphocyte subsets.After 24 weeks of treatment, sPD-1/sPD-L1 in peripheral blood of patients in the treatment group showed no significant correlation with the expression levels of CD3+T, CD4+T and CD8+T lymphocyte subsets.Conclusion Entecavir therapy can not only inhibit HBV DNA replication, but also help regulate the expression levels of sPD-1, sPD-L1 and T lymphocytes in CHB patients circulating blood.At the same time, sPD-1/sPD-L1 may be involved in the regulation of the immune function of CHB patients, which can reflect the degree of liver tissue damage, virus replication level and disease change direction to a certain extent.