The correlation between sPD-1/sPD-L1 and T cells in patients with HBV-related acute-on-chronic liver failure
古丽沙提·海米提 1朱玥洁 2谢忻汝 1郭文宏 1丁剑冰 3鲁晓擘 4张峰波1
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作者信息
1. 新疆医科大学第一附属医院检验科,新疆 乌鲁木齐 830011
2. 新疆医科大学第一附属医院生殖助孕科,新疆 乌鲁木齐 830011
3. 新疆医科大学省部共建中亚高发病成因与防治国家重点实验室,新疆 乌鲁木齐 830003
4. 新疆医科大学第一附属医院感染病·肝病中心,新疆 乌鲁木齐 830011
折叠
摘要
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HBV-ACLF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/sPD-L1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.
Abstract
Objective:To investigate the expression levels of soluble programmed cell death protein1(sPD-1)and soluble pro-grammed 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-β and 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-β in 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-β and 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-β and 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.
关键词
慢加急性肝衰竭/T细胞/可溶性程序性死亡蛋白-1/可溶性程序性死亡蛋白配体-1
Key words
Acute-on-chronic liver failure/T lymphocytes/Soluble programmed death protein-1/Soluble programmed death protein ligand-1