耐多药肺结核外周血Treg细胞表面CTLA-4、PD-1和ICOS表达及意义  

Expressions of CTLA-4,PD-1 and ICOS on surface of peripheral blood Treg cells in patients with multidrug-resistant tuberculosis and clinical significance

作　　者：黄远江 蔡暖暖 陈琼 HUANG Yuan-jiang;CAI Nuan-nuan;CHEN Qiong(The Second Affiliated Hospital of Hainan Medical University,Haikou,Hainan 570216,China;不详)

机构地区：[1]海南医学院附属第二医院结核病科,海南海口570216 [2]海南省人民医院呼吸科,海南海口570311

出　　处：《中华医院感染学杂志》2022年第21期3268-3272,共5页Chinese Journal of Nosocomiology

基　　金：海南省医药卫生科研基金资助项目(2001320241A2007)。

摘　　要：目的探究耐多药肺结核(MDR-TB)患者外周血调节性T细胞(Treg)表面细胞毒T淋巴细胞相关抗原4(CTLA-4)、程序性死亡因子-1(PD-1)和可诱导共刺激分子(ICOS)的表达水平及临床意义。方法回顾性分析2016年6月-2020年6月海南医学院附属第二医院收治的763例MDR-TB患者(MDR-TB组)、531例非耐药肺结核患者(DS-TB组)和450名健康体检者(对照组)的临床资料,比较三组、MDR-TB组中不同预后患者外周血Treg细胞含量和Treg细胞表面CTLA-4、PD-1、ICOS的表达水平。结果MDR-TB组和DS-TB组γ干扰素(IFN-γ)、白细胞介素(IL)-4、IL-5水平均低于对照组(P<0.05);三组IL-10、IL-17、外周血Treg细胞含量和CTLA-4、PD-1表达水平比较,MDR-TB组>DS-TB组>对照组(P<0.05);MDR-TB组和DS-TB组ICOS表达水平高于对照组(P<0.05)。MDR-TB患者中,死亡组CTLA-4、PD-1和ICOS表达水平均高于生存组(P<0.05)。受试者工作特征(ROC)曲线分析结果显示,外周血Treg细胞表面CTLA-4、PD-1和ICOS诊断MDR-TB的曲线下面积(AUC)分别为0.859、0.733和0.616,CTLA-4、PD-1水平在诊断MDR-TB方面均有统计学意义(P<0.05),ICOS水平在诊断MDR-TB方面无统计学差异;预测MDR-TB患者预后的AUC值分别为0.719、0.780和0.795,均有统计学意义(P<0.05)。结论MDR-TB存在较为严重的免疫抑制,外周血Treg细胞表面CTLA-4、PD-1和ICOS可能参与MDR-TB的发生发展,三者对于MDR-TB的诊断及患者的预后具有一定预测价值。OBJECTIVE To explore the expression levels of cytotoxic T lymphocyte-associated antigen 4(CTLA-4),programmed death-1(PD-1)and inducible costimulatory molecule(ICOS)on surface of peripheral blood regulatory T(Treg)cells in patients with multidrug-resistant tuberculosis(MDR-TB)and analyze the clinical significance.METHODS A total of 763 patients with MDR-TB who were treated in the Second Affiliated Hospital of Hainan Medical University from Jun 2016 to Jun 2020 were assigned as the MDR-TB group,531 patients with drug-susceptible tuberculosis(DS-TB)were chosen as the DS-TB group,and 450 healthy people who received physical examination were set as the control group;the clinical data of the study objects were retrospectively analyzed.The peripheral blood Treg cell level and the expression levels of CTLA-4,PD-1 and ICOS on surface of Treg cells were observed and compared among the three groups and among the patients with different treatment outcomes in the MDR-TB group.RESULTS The levels of interferon-γ(IFN-γ),interleukin-(IL-4)and IL-5 of the MDR-TB group and the DS-TB group were lower than those of the control group(P<0.05).The IL-10 level,IL-17 level,peripheral blood Treg cell content,CTLA-4 level and PD-1 level were higher in the MDR-TB group than in the DS-TB group than in the control group(P<0.05);the expression level of ICOS of the MDR-TB group and the DS-TB group was higher than that of the control group(P<0.05).Among the MDR-TB patients,the expression levels of CTLA-4,PD-1 and ICOS of the death group were higher than those of the survival group(P<0.05).The result of receiver operating characteristic(ROC)curve analysis showed that the areas under curves(AUCs)of CTLA-4,PD-1 and ICOS on surface of peripheral blood Treg cells were respectively 0.859,0.733 and 0.616 in diagnosis of MDR-TB,and there was significant difference in diagnosis of MDR-TB between the CTLA-4 level and the PD-1 level(P<0.05),while there was no significant difference in diagnosis of MDR-TB with ICOS level;the AUCs were respectively 0.719,0.

关 键 词：耐多药肺结核 调节性T细胞 细胞毒T淋巴细胞相关抗原4 程序性死亡因子-1 可诱导共刺激分子 

分 类 号：R521[医药卫生—内科学]