Zhao Huimin, Chen Zhenyan, Lowrie Douglas B, Hu Zhidong, Lu Shuihua, Fan Xiao-Yong
Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China.
Department of Clinical Laboratory, Gansu Provincial Maternity and Child-care Hospital (Gansu Provincial Central Hospital), Lanzhou, Gansu, China.
Infection. 2025 Mar 17. doi: 10.1007/s15010-024-02454-z.
A leading cause of death from infectious diseases worldwide is tuberculosis (TB), and it often arises from latent infection. New diagnostic tests for latent tuberculosis infection (LTBI) are needed. Therefore, this study aimed to identify novel biomarker signatures in whole human blood to distinguish between active tuberculosis (ATB) and LTBI.
Two LEGENDplex kits were used to evaluate the secretion levels of 20 cytokines triggered by ESAT-6/CFP10 antigen in whole blood of ATB, LTBI, and healthy controls, and to search for cytokine combinations utilized to distinguish between ATB and LTBI.
IL-8, IL-18, IL-33, MCP-1, MIG (baseline levels); IL-8, IL-33, IL-1β, MCP-1, MIG, IL-10, I-TAC (ESAT-6/CFP10-stimulated levels); and IL-18, IL-33, IL-1β, IL-10, TNF-α (ESAT-6/CFP10-stimulated minus baseline levels) had the potential to distinguish ATB from LTBI. Our data shows that the sensitivity and specificity of targeted IL-8 and IL-33 distinguishing between ATB and LTBI were 83.3% and 93.75%, and the diagnostic accuracy was 89.28%, and the sensitivity and specificity of targeted IL-18 and IL-33 distinguishing between ATB and LTBI were 91.67% and 81.25%, with the diagnostic accuracy was 85.71%.
Our data suggest that IL-8/IL-33 and IL-33/IL-18 together can be utilized as immunological markers to differentiate between LTBI and ATB. A novel TB diagnostic protocol was established, offering novel perspectives to create better tests.
全球范围内，传染病导致死亡的一个主要原因是结核病（TB），且它常源于潜伏感染。因此需要新型潜伏性结核感染（LTBI）诊断测试。所以，本研究旨在确定全血中的新型生物标志物特征，以区分活动性结核病（ATB）和LTBI。
使用两种LEGENDplex试剂盒评估ESAT-6/CFP10抗原触发的20种细胞因子在ATB、LTBI和健康对照全血中的分泌水平，并寻找用于区分ATB和LTBI的细胞因子组合。
白细胞介素-8（IL-8）、白细胞介素-18（IL-18）、白细胞介素-33（IL-33）、单核细胞趋化蛋白-1（MCP-1）、γ干扰素诱导单核因子（MIG）（基线水平）；IL-8、IL-33、白细胞介素-1β（IL-1β）、MCP-1、MIG、白细胞介素-10（IL-10）、γ干扰素诱导的T细胞α趋化因子（I-TAC）（ESAT-6/CFP10刺激水平）；以及IL-18、IL-33、IL-1β、IL-10、肿瘤坏死因子-α（TNF-α）（ESAT-6/CFP10刺激减去基线水平）有区分ATB和LTBI的潜力。我们的数据显示，靶向IL-8和IL-33区分ATB和LTBI的敏感性和特异性分别为83.3%和93.75%，诊断准确率为89.28%，靶向IL-18和IL-33区分ATB和LTBI的敏感性和特异性分别为91.67%和81.25%，诊断准确率为85.71%。
我们的数据表明，IL-8/IL-33和IL-33/IL-18共同可用作免疫标志物以区分LTBI和ATB。建立了一种新型结核病诊断方案，为开发更好的检测方法提供了新视角。
