慢性乙型肝炎临床治愈者的血清sPD-1和sPD-L1水平及临床特点  

Serum levels of soluble programmed death-1 and soluble programmed death-ligand 1 in chronic hepatitis B patients with clinical cure and their clinical features

作　　者：谭宁 刘建湘[1] 亢倩 潘家莉 韩一凡 陈宏宇 徐小元[1] TAN Ning;LIU Jianxiang;KANG Qian;PAN Jiali;HAN Yifan;CHEN Hongyu;XU Xiaoyuan(Department of Gastroenterology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院消化内科,北京100034

出　　处：《临床肝胆病杂志》2023年第1期50-55,共6页Journal of Clinical Hepatology

基　　金：北京市科技计划项目(D171100003117005,D161100002716003)。

摘　　要：目的对慢性乙型肝炎(CHB)临床治愈者的血清可溶性程序性死亡蛋白-1(sPD-1)和程序性死亡蛋白配体-1(sPD-L1)进行分析,并通过流式细胞技术分析与体内PD-1^(+)淋巴细胞的相关性,探究CHB临床治愈者体内病毒特异性免疫的恢复情况。方法纳入2022年1月—5月在北京大学第一医院门诊诊断的CHB临床治愈者26例、CHB初治患者26例和健康对照者26例,收集临床数据和外周血样本。使用ELISA法对血清sPD-1和sPD-L1进行检测。使用流式细胞技术分析外周血淋巴细胞PD-1分布。将CHB临床治愈者分别与CHB初治患者和健康对照者进行比较。非正态分布计量资料3组间比较采用Kruskal-Wallis H检验,计数资料3组间比较采用χ^(2)检验。使用Pearson相关或Spearman相关进行两个连续变量之间的相关性分析。结果CHB临床治愈者26例平均抗病毒治疗时间约8.33年,抗病毒治疗药物均为恩替卡韦。临床治愈者的sPD-1和sPD-L1水平显著高于健康对照者(P值均<0.05),PD-1^(+)细胞/淋巴细胞、PD-1^(+)CD8^(+)T淋巴细胞/淋巴细胞显著低于CHB初治患者(P值均<0.05)。CHB初治患者血清sPD-1、sPD-L1与HBsAg水平均呈中等程度负相关(r值分别为-0.524、-0.583,P值均<0.05)。血清sPD-1、sPD-L1水平和PD-1^(+)CD8^(+)T淋巴细胞/淋巴细胞具有中等程度的正相关(r值分别为0.535、0.419,P值均<0.05)。CHB临床治愈者血清sPD-1和sPD-L1水平和年龄、性别、ALT、T淋巴细胞/淋巴细胞、CD8^(+)T淋巴细胞/淋巴细胞、PD-1^(+)细胞/淋巴细胞、PD-1^(+)CD8^(+)T淋巴细胞/淋巴细胞均无相关性(P值均>0.05)。结论CHB初治患者血清sPD-1、sPD-L1水平主要与外周血耗竭型CD8^(+)T淋巴细胞有关。CHB临床治愈者血清sPD-1、sPD-L1水平与外周血耗竭型CD8^(+)T淋巴细胞相关性不显著。Objective To investigate the serum levels of soluble programmed death-1(sPD-1)and soluble programmed death-ligand 1(sPD-L1)in chronic hepatitis B(CHB)patients with clinical cure,the correlation between programmed death-1(PD-1)and lymphocytes by flow cytometry,and the recovery of hepatitis B virus(HBV)-specific immunity.Methods A total of 26 CHB patients with clinical cure,26 treatment-naive CHB patients,and 26 healthy controls who were diagnosed at the outpatient service of Peking University First Hospital from January to May of 2022 were enrolled,and related clinical data and peripheral blood samples were collected.ELISA was used to measure the serum levels of sPD-1 and sPD-L1,and flow cytometry was used to measure the expression of PD-1 in peripheral blood lymphocytes.CHB patients with clinical cure were compared with the treatment-naive CHB patients and the healthy controls.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups,and the chi-square test was used for comparison of categorical data between groups.The Pearson correlation analysis or the Spearman correlation analysis was used to investigate the correlation between two continuous variables.Results For the 26 CHB patients with clinical cure,the mean time of antiviral therapy was 8.33 years,with entecavir as the antiviral drug.The CHB patients with clinical cure had significantly higher levels of sPD-1 and sPD-L1 than the healthy controls(P<0.05)and significantly lower percentages of PD-1^(+)cells/lymphocytes and PD-1^(+)CD8^(+)T cells/lymphocytes than the treatment-naive CHB patients(P<0.05).In the treatment-naive CHB patients,the serum levels of sPD-1 and sPD-L1 were moderately negatively correlated with HBsAg level(r=-0.524 and-0.583,both P<0.05).The serum levels of sPD-1 and sPD-L1 were moderately positively correlated with PD-1^(+)CD8^(+)T cells/lymphocytes(r=0.535 and 0.419,both P<0.05).In the CHB patients with clinical cure,the serum levels of sPD-1 and sPD-L1 were not correlated with a

关 键 词：乙型肝炎 慢性 可溶性程序性死亡蛋白-1 CD8阳性T淋巴细胞 

分 类 号：R512.62[医药卫生—内科学]