HBV相关慢加急性肝衰竭患者sPD-1/sPD-L1与T细胞的相关性分析

The correlation between sPD⁃1/sPD⁃L1 and T cells in patients with HBV⁃related acute⁃on⁃chronic liver failure

目的:探讨乙型肝炎病毒(hepatitis B virus,HBV)相关慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)患者病程中可溶性程序性死亡蛋白1(soluble Programmed cell death protein1,sPD-1)、可溶性程序性死亡蛋白配体-1(soluble Programmed cell death ligand1,sPD-L1)、T淋巴细胞、白细胞介素-10(interleukin-10,IL-10)和转化生长因子-β(transforming growth factor-β,TGF-β)的表达水平及各指标间的相关性。方法:收集71例确诊为HBV-ACLF患者的资料及外周血标本,根据研究对象28 d的随访结果,分为存活组40例和死亡组31例。采用流式细胞术检测研究对象外周血CD4+T及CD8+T细胞的比例。采用流式液相多重蛋白定量(cytometric bead array,CBA)技术检测sPD-1和sPD-L1的表达。采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测TGF-β和IL-10的表达。Pearson法分析HBVACLF患者血清中sPD-1/sPD-L1与患者MELD评分、T细胞及细胞因子水平的相关性。结果:死亡组外周血及血清中CD4+T细胞百分比、sPD-1、sPD-L1、IL-10和TGF-β高于存活组,而CD8+T细胞百分比低于存活组(P均<0.05)。经相关性分析显示,sPD-1水平与IL-10、TGF-β和CD4+T细胞百分比呈正相关,与CD8+T细胞百分比呈负相关。sPD-L1水平与终末期肝病模型(model for end-stage liver disease,MELD)评分、IL-10、TGF-β和CD4+T呈正相关,与CD8+T细胞比例呈负相关(P均<0.05)。结论:sPD-1/sPDL1可能参与了HBV-ACLF发生、发展过程中的免疫应答,通过综合考虑患者sPD-1和sPD-L1水平可以为HBV-ACLF患者开展及时有效的治疗提供一定的参考。

Objective:To investigate the expression levels of soluble programmed cell death protein1(sPD-1)and soluble programmed cell death ligand1(sPD-L1),T cells,interleukin-10(IL-10)and transforming growth factor-β(TGF-β)in peripheral blood of patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF)and the correlation between each in-dex.Methods:According to the inclusion and exclusion criteria,the data and peripheral blood samples of 71 patients diagnosed with HBV-ACLF were collected.According to the 28-day follow-up,the subjects were divided into survival group(40 cases)and death group(31 cases).The proportion of CD4+T and CD8+T cells in peripheral blood was detected by flow cytometry.The expression levels of sPD-1 and sPD-L1 in serum were detected by cytometric bead array(CBA).Enzyme-linked immunosorbent assay was used to detect the expression of TGF-βand IL-10 in the serum of the subjects.Pearson method was used to analyze the correlation between serum sPD-1 and sPD-L1 and MELD score,T lymphocyte level,and cytokine level in patients with HBV-ACLF.Results:The percentages of CD4+T cells,sPD-1,sPD-L1,IL-10 and TGF-βin peripheral blood and serum of the death group were higher than those of the survival group,while the percentage of CD8+T cells was lower than that of the survival group(all P<0.05).Correlation analysis showed that the level of sPD-1 was positively correlated with the percentages of IL-10,TGF-βand CD4+T cells,and negatively correlated with the percentage of CD8+T cells.The level of sPD-L1 was positively correlated with model for end-stage liver disease score,IL-10,TGF-βand CD4+T,and negatively correlated with the propor-tion of CD8+T cells(all P<0.05).Conclusion:sPD-1 and sPD-L1 may be involved in the immune response during the occur-rence and development of HBV-ACLF.By comprehensively considering the levels of sPD-1 and sPD-L1,it can provide certain clinical value for timely and effective treatment of HBV-ACLF patients.