三种蛋白诊断结核分枝杆菌感染的价值研究  

The value of three proteins in diagnosing Mycobacterium tuberculosis infection

作　　者：张慕丽 孙照刚[2] 曹廷明[2] 谢忠尧[1] Zhang Muli;Sun Zhaogang;Cao Tingming;Xie Zhongyao(Department of Healthcare-Associated Infection Management,Beijing Chest Hospital,Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China;Translational Medicine Center,Beijing Chest Hospital,Capital Medical University/Beijing Key Laboratory in Drug Resistant Tuberculosis Research/Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China)

机构地区：[1]首都医科大学附属北京胸科医院感染管理处/北京市结核病胸部肿瘤研究所,北京101149 [2]首都医科大学附属北京胸科医院转化医学研究室/北京市结核病胸部肿瘤研究所耐药结核病研究北京市重点实验室,北京101149

出　　处：《中国防痨杂志》2024年第7期808-814,共7页Chinese Journal of Antituberculosis

基　　金：北京市高层次公共卫生人才项目(G2024-2-005)。

摘　　要：目的:探讨Krüppel样转录因子2(krüppel-like transcription factor 2,KLF2)、鸟苷酸结合蛋白5(guanylate-binding protein 5,GBP5)、双特异性磷酸酶3(dual specificity phosphatase 3,DUSP3)等3种蛋白及其不同组合对于结核分枝杆菌(Mycobacterium tuberculosis,MTB)感染的诊断价值。方法:选取2023年1—3月首都医科大学附属北京胸科医院就诊患者和同期进行健康体检的人群作为研究对象,根据结核病诊断标准将研究对象分为活动性结核病(ATB)组(145例)、结核分枝杆菌潜伏感染(LTBI)组(145例)、健康对照(HC)组(200名)。使用酶联免疫吸附试验(ELISA)检测研究对象血清中KLF2、GBP5、DUSP3蛋白水平[450 nm波长吸光度值;中位数(四分位数)],采用受试者工作特征曲线分析各蛋白单独或联合诊断MTB感染的价值。结果:KLF2在HC组的蛋白水平为0.317(0.198,0.496),明显高于ATB组的0.234(0.160,0.297)及LTBI组的0.224(0.145,0.320),差异均有统计学意义(P<0.001)。GBP5在ATB组的蛋白水平为0.327(0.259,0.402),明显高于LTBI组的0.196(0.150,0.273)及HC组的0.180(0.125,0.281),差异均有统计学意义(P<0.001)。DUSP3在ATB组的蛋白水平为0.329(0.223,0.458),明显高于LTBI组的0.213(0.160,0.248)及HC组的0.196(0.132,0.297),差异均有统计学意义(P<0.001)。GBP5与DUSP3双蛋白组合区分ATB和LTBI的诊断效能[曲线下面积(AUC)为0.800]优于KLF2(AUC为0.534)、GBP5(AUC为0.761)、DUSP3(AUC为0.720)等单一蛋白及其不同组合的诊断效能,最大约登指数下的敏感度为73.79%,特异度为75.86%;GBP5、DUSP3双蛋白组合区分ATB和HC的诊断效能(AUC为0.781)优于KLF2(AUC为0.629)、GBP5(AUC为0.740)、DUSP3(AUC为0.716)等单一蛋白及其不同组合的诊断效能,最大约登指数下的敏感度为77.93%,特异度为71.50%;三种蛋白及其不同组合区分LTBI与HC的诊断效能较差,其AUC均小于0.700。结论:研发基于蛋白水平的MTB感染免疫检测方法存在可能性,蛋白联和应用可提高诊断效�Objective:To investigate the diagnostic efficacy of three proteins—Krüppel-like transcription factor 2(KLF2),guanylate-binding protein 5(GBP5),and dual specificity phosphatase 3(DUSP3)—and their assorted combinations in the detection of Mycobacterium tuberculosis(MTB)infection.Methods:Between January and March 2023,patients from Beijing Chest Hospital,Capital Medical University,and individuals undergoing concurrent health examinations were enrolled as study participants.Based on established tuberculosis diagnostic criteria,participants were categorized into three groups:active tuberculosis(ATB)group,consisting of 145 cases;latent tuberculosis infection(LTBI)group,also comprising 145 cases;and a healthy control(HC)group,which included 200 cases.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify the serum levels of KLF2,GBP5,and DUSP3 at 450 nm wavelength absorbance,with results reported as median(interquartile range).The diagnostic potential of each protein,individually and in combination,was analyzed for detecting MTB infection using subject working characteristic curves.Results:Serum levels of KLF2 in the HC group were 0.317(0.198,0.496),significantly higher than those in the ATB group at 0.234(0.160,0.297)and in the LTBI group at 0.224(0.145,0.320),demonstrating statistical significance(P<0.001).Similarly,GBP5 levels in the ATB group were 0.327(0.259,0.402),significantly higher than those in the LTBI group at 0.196(0.150,0.273)and in the HC group at 0.180(0.125,0.281),with statistical significance(P<0.001).The serum level of DUSP3 in the ATB group was 0.329(0.223,0.458),significantly exceeding those in the LTBI group at 0.213(0.160,0.248)and in the HC group at 0.196(0.132,0.297),with statistical significance(P<0.001).Furthermore,the diagnostic performance of the dual protein combination of GBP5 and DUSP3 in differentiating ATB from LTBI,with an area under the curve(AUC)of 0.800,was found to be superior to that of single proteins and their various combinations,such as KLF2(AUC of 0.534),GBP5(A

关 键 词：分枝杆菌 结核 感染 免疫测定 诊断 鉴别 

分 类 号：R52[医药卫生—内科学]