结核抗原特异细胞因子在HIV感染者中诊断结核病的临床价值评估  

The performance of Mycobacterium tuberculosis-specific antigens-induced cytokines in the diagnosis of tuberculosis among HIV-infected individuals

作　　者：姚明旭 王泽琦 宋瑞雪 贾红彦[1] 孙琦[1] 张蓝月 杜博平 张宗德[1] 汪雯 吴亮 潘丽萍[1] Yao Mingxu;Wang Zeqi;Song Ruixue;Jia Hongyan;Sun Qi;Zhang Lanyue;Du Boping;Zhang Zongde;Wang Wen;Wu Liang;Pan Liping(Department of Molecular Biology,Beijing Key Laboratory for Drug-Resistant Tuberculosis Research,Beijing Chest Hospital,Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China;Department of Infectious Diseases,Beijing You’an Hospital,Capital Medical University,Beijing 100069,China;Center of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China)

机构地区：[1]首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所分子生物学实验室/耐药结核病研究北京市重点实验室,北京101149 [2]首都医科大学附属北京佑安医院感染中心,北京100069 [3]首都医科大学附属北京地坛医院感染性疾病诊疗中心,北京100015

出　　处：《中国防痨杂志》2025年第5期605-612,共8页Chinese Journal of Antituberculosis

基　　金：北京市自然科学基金(L234055);高层次公共卫生技术人才建设项目培养计划(学科骨干-03-37);北京市适宜技术推广项目(BHTPP2024084)。

摘　　要：目的:评估HIV感染者中应用结核分枝杆菌(Mycobacterium tuberculosis,MTB)抗原特异细胞因子和趋化因子诊断结核病的临床价值。方法:前瞻性纳入2021年12月至2024年6月在首都医科大学附属北京地坛医院、首都医科大学附属北京佑安医院就诊的HIV感染者132例,所有患者均采集外周血12 ml,完成结核感染T细胞检测,并收集MTB抗原刺激和未刺激的全血,在全自动细胞提取仪完成RNA提取,采用SYBG引物法完成白细胞介素-2(IL-2)、IL-5、IL-18、IL-24、单核细胞趋化蛋白-1(MCP-1)、单核细胞趋化蛋白-2(MCP-2)、单核细胞趋化蛋白-3(MCP-3)、趋化因子CXC配体9(CXCL9)、趋化因子CXC配体10(CXCL10)、CC基序趋化因子配体19(CCL19)、巨噬细胞集落刺激因子(CSF-1)和γ-干扰素(IFNG)等基因的qPCR检测,分析上述因子在结核组和非结核组间的表达差异,采用Lasso回归模型筛选特征性指标,并绘制受试者工作特征曲线(receiver operating curve,ROC),评价上述因子及组合在HIV感染者中诊断结核病的临床价值。结果:根据研究对象临床诊断信息,剔除诊断不明者35例,最终97例纳入分析,其中,结核病患者44例,非结核病患者53例。结核病组MTB抗原特异的IL-18和IFNG的ΔΔCt值[中位数(四分位数)]分别为0.5601(-0.0207,1.2880)和1.0130(0.0284,3.9950),与非结核病组[分别为0.0364(-0.6420,0.7438)和0.3727(-0.5992,1.2460)]相比,均明显上调,差异均有统计学意义(Z值分别为-2.284和-1.989,P值分别为0.018和0.028);而结核病组MTB抗原特异的MCP-1、MCP-2、CXCL9、CXCL10的ΔΔCt值[中位数(四分位数)]分别为-1.1660(-1.8920,-0.5699)、-1.4640(-3.5530,0.5763)、-1.7680(-6.3950,-0.2807)、-1.8260(-4.6000,-0.0814),与非结核病组[分别为-0.5803(-1.0040,0.1794)、-0.2367(-1.3010,0.7079)、0.2730(-1.2750,1.8360)、-0.2505(-0.6528,0.9105)]相比,均明显下调,差异均有统计学意义(Z值分别为3.162、2.529、3.745、3.743,P值分别为0.003、0.014、0.001、<0.001Objective:To evaluate the clinical value of Mycobacterium tuberculosis(MTB)-specific antigens-induced cytokines in the diagnosis of tuberculosis in HIV-infected individuals.Methods:A total of 132 HIV-infected individuals who visited Beijing Ditan Hospital and Beijing You’an Hospital from December 2021 to June 2024 were prospectively included as study subjects.Twelve milliliters of peripheral blood were collected from each patient,and the interferon-γrelease assays were performed on peripheral blood.The whole blood with or without MTB-specific antigens stimulation was collected and the total RNA was extracted automatically,and then the expression levels of cytokines(interleukin-2(IL-2),IL-5,IL-18,IL-24,monocyte chemoattractant protein-1(MCP-1),MCP-2,MCP-3,chemokine CXC ligand 9(CXCL9),chemokine CXC ligand 10(CXCL10),CC motif chemokine ligand 19(CCL19),macrophage colony-stimulating factor(CSF-1),and interferon-γ(IFNG))were tested by SYBG-qPCR.The differences in the expression level of cytokines were analyzed between the TB group and the non-TB group,and the performance of cytokines in differentiating TB was investigated by receiver operating curve(ROC)analysis.Lasso analysis was also performed to evaluate the combined performance of the cytokines in identifying TB patients among HIV-infected individuals.Results:According to the clinical diagnosis information of the subjects,35 cases with unknown diagnosis were excluded,and 97 cases were finally included in the analysis,including 44 cases of TB patients and 53 cases of non-TB patients.TheΔΔCt values(median(quartile))of MTB-antigen specific IL-18 and IFNG in the TB group were 0.5601(-0.0207,1.2880)and 1.0130(0.0284,3.9950),respectively,which were significantly higher than those in the non-TB group(0.0364(-0.6420,0.7438)and 0.3727(-0.5992,1.2460),respectively),with statistically significant differences(Z values were-2.284 and-1.989,P values were 0.018 and 0.028).TheΔΔCt values(median(quartile))of MCP-1,MCP-2,CXCL9,and CXCL10 in the TB group were-1.1660(-1.8920

关 键 词：分枝杆菌 结核 HIV 感染 细胞因子类 诊断 鉴别 

分 类 号：R52[医药卫生—内科学]