HIV/AIDS患者病毒载量与CD8+T细胞活化及耗竭水平的相关性研究  

Study on the correlation between viral load and activation and exhaustion levels of CD8+T cells in HIV/AIDS patients

作　　者：詹洁琼 宋黎黎[2] 林怡[3] 董原[3] 王宇[1] 褚维[1] Zhan Jieqiong;Song Lili;Lin Yi;Dong Yuan;Wang Yu;Chu Wei(Department of Microbiological Laboratory,Centers for Disease Control and Prevention of Huangpu District,Shanghai200023,China;Centers for Disease Control and Prevention of Huangpu District,Shanghai200023,China;Division of Tuberculosis and HIV/AIDS Control and Prevention,Shanghai Municipal Center for Disease Control and Prevention,Shanghai200336,China)

机构地区：[1]上海市黄浦区疾病预防控制中心微生物实验室,上海200023 [2]上海市黄浦区疾病预防控制中心,上海200023 [3]上海市疾病预防控制中心结核病与艾滋病防治所,上海200336

出　　处：《中华预防医学杂志》2024年第11期1690-1696,共7页Chinese Journal of Preventive Medicine

基　　金：上海市疾病预防控制青年骨干人才培养项目(22QNGG24);2023年度上海市黄浦区卫生健康委员会科研项目(HLM202329);2023年度黄浦区医学培育专科建设黄浦区公共卫生应急响应(重点)实验室(2023PYZK04)。

摘　　要：目的探讨并分析人类免疫缺陷病毒(HIV)/获得性免疫缺陷综合征(AIDS)患者外周血CD8^(+)T细胞上CD38、HLA-DR和程序性死亡蛋白-1(PD-1)的表达水平与HIV-1 RNA病毒载量、免疫活化和耗竭的相关性。方法纳入HIV/AIDS患者81例(未接受抗病毒治疗者64例,接受治疗者17例)、同期40例健康捐献者作为对照组。采用流式细胞术分析CD4^(+)T淋巴细胞计数和CD8^(+)T细胞上活化标志物CD38、HLA-DR和凋亡标志物PD-1的表达水平,通过实时荧光定量聚合酶链反应定量检测HIV-1感染者血浆中的HIV-1 RNA。采用方差分析比较HIV/AIDS患者与健康对照组CD8^(+)T细胞CD38、HLA-DR、PD-1的表达水平;采用Spearman相关性分析不同T淋巴细胞计数与HIV RNA病毒载量的相关性以及病毒载量与外周血CD8^(+)T细胞CD38、HLA-DR和PD-1的相关性。结果81例HIV/AIDS患者中,男性69例(85.19%),女性12例(14.81%),年龄M(Q1,Q3)为58(36.5,65.0)岁;年龄超过55岁以上的HIV/AIDS患者60例(74.07%),18~55岁HIV/AIDS患者21例(25.93%)。方差分析结果显示,与健康人群对照组相比,HIV/AIDS患者CD38、HLA-DR、PD-1在CD8^(+)T细胞上表达水平增加(均P<0.05),并且在CD4^(+)T细胞计数小于350 cells/μl的患者中,CD38、HLA-DR与PD-1的表达增加更高(均P<0.05)。Spearman相关性分析结果显示,HIV/AIDS患者CD4^(+)、CD4^(+)/CD8^(+)与病毒载量呈负相关(r分别为-0.407、-0.378,均P<0.05),CD8^(+)与病毒载量呈正相关(r=0.356,P<0.05);当HIV RNA水平≤105 CPs/ml时,HIV RNA水平与CD8^(+)T细胞CD38、HLA-DR、PD-1的表达水平无相关性(均P>0.05),当HIV RNA水平>10^(5) CPs/ml时,HIV RNA水平与CD8^(+)T细胞CD38、HLA-DR、PD-1的表达水平呈正相关(r分别为0.412、0.387、0.395,均P<0.05)。结论HIV/AIDS患者外周血CD8^(+)T细胞上CD38、HLA-DR活化水平升高、PD-1表达上调;当病毒载量较高时,患者HIV RNA病毒载量与CD8^(+)T细胞活化和耗竭水平呈正相关。ObjectiveTo investigate and analyze the correlation between the expression levels of CD38,HLA-DR and programmed cell death-1(PD-1)on peripheral blood CD8^(+)T cells and HIV-1 RNA viral load,immune activation and exhaustion in patients with human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS).MethodsA total of 81 HIV/AIDS patients(64 without antiretroviral therapy and 17 with therapy)and 40 healthy donors in the same period were enrolled as the control group.Flow cytometry was used to analyze the CD4^(+)T lymphocyte count and the expression levels of activation markers CD38 and HLA-DR and apoptosis marker PD-1 on CD8^(+)T cells.HIV-1 RNA in the plasma of HIV-1 infected patients was quantitatively detected by real-time fluorescence quantitative polymerase chain reaction.Variance analysis was used to compare the expression levels of CD38,HLA-DR and PD-1 on CD8^(+)T cells between HIV/AIDS patients and healthy controls.Spearman correlation analysis was used to analyze the correlation between different T lymphocyte counts and HIV RNA viral load,and the correlation between HIV RNA viral load and peripheral blood CD8^(+)T cell CD38,HLA-DR and PD-1.ResultsAmong the 81 HIV/AIDS patients,69(85.19%)were males and 12(14.81%)were females,with an age M(Q 1,Q 3)of 58(36.5,65.0)years.There were 60 HIV/AIDS patients over 55 years old(74.07%)and 21 HIV/AIDS patients between 18 and 55 years old(25.93%).The results of variance analysis showed that compared with the healthy control group,the expression levels of CD38,HLA-DR and PD-1 on CD8^(+)T cells in HIV/AIDS patients increased,and the differences were statistically significant(all P<0.05).In addition,the expression of CD38,HLA-DR and PD-1 increased significantly in patients with CD4^(+)T cell count less than 350 cells/μl,and the differences were statistically significant(all P<0.05).Spearman correlation analysis showed that CD4^(+)and CD4^(+)/CD8^(+)were negatively correlated with viral load in HIV/AIDS patients(r=-0.407 and-0.378,respectively,both P<0.05),a

关 键 词：HIV RNA CD8+T细胞 细胞活化 细胞凋亡 

分 类 号：R512.91[医药卫生—内科学]