Yang Jiarong, Lv Zizheng, Liu Liguo, Zhang Han, Hu Jie, Geng Xingzhu, Xin Henan, Liu Zisen, Gao Lei, Zhang Xiaobing, Xu Yanli, Liu Rongmei, Jin Qi, Zheng Jianhua
NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Research ward, Beijing Chest Hospital, Capital Medical University/ Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China.
EBioMedicine. 2025 Oct;120:105945. doi: 10.1016/j.ebiom.2025.105945. Epub 2025 Sep 27.
Tuberculosis (TB) is one of the deadliest infectious diseases worldwide, causing millions of new cases and deaths annually. Rapid and accurate TB diagnostics are essential for TB control, yet current methods do not fully meet global needs. Peripheral blood neutrophils play a critical role in TB infection and represent a promising source of diagnostic markers.
We conducted a cross-sectional proteomic analysis to characterise neutrophil protein profiles in individuals with active TB (ATB), latent TB infection (LTBI), and healthy controls (HC). Stringent criteria were applied to identify differentially expressed proteins (DEPs) among these groups. Transcriptomic data were integrated to perform pathway enrichment analysis of DEPs. Three DEPs (B2M, TXN, and PRDX5) were further validated as candidate diagnostic biomarkers for Mycobacterium tuberculosis (MTB) infection using automated western blotting in a cohort of 319 individuals, including 71 ATB, 142 LTBI, and 106 HC.
Hundreds of DEPs were identified across the three groups. Integrated transcriptomic analysis revealed significant enrichment of DEPs in the NOD-like receptor signalling pathway. Receiver operating characteristic analysis of the three-protein combination (B2M, TXN, and PRDX5) yielded an area under the curve of 0.9847, with a sensitivity of 95.11% and a specificity of 96.23% for detecting MTB infection.
This study presents a comprehensive proteomic profile of neutrophils under different MTB infection states, and this three-protein combination may assist in the diagnosis of MTB infection.
This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-037) and the National Science and Technology Major Project of China (20212017ZX10201301-002-003).
结核病是全球最致命的传染病之一，每年导致数百万新发病例和死亡。快速准确的结核病诊断对于结核病控制至关重要，但目前的方法尚未完全满足全球需求。外周血中性粒细胞在结核病感染中起关键作用，是有前景的诊断标志物来源。
我们进行了一项横断面蛋白质组学分析，以表征活动性结核病（ATB）、潜伏性结核感染（LTBI）和健康对照（HC）个体的中性粒细胞蛋白质谱。应用严格标准来鉴定这些组之间的差异表达蛋白（DEP）。整合转录组数据以对DEP进行通路富集分析。在包括71例ATB、142例LTBI和106例HC的319名个体队列中，使用自动蛋白质印迹法进一步验证了三种DEP（B2M、TXN和PRDX5）作为结核分枝杆菌（MTB）感染的候选诊断生物标志物。
在三组中鉴定出数百种DEP。整合转录组分析显示DEP在NOD样受体信号通路中显著富集。对三种蛋白质组合（B2M、TXN和PRDX5）的受试者工作特征分析得出曲线下面积为0.9847，检测MTB感染的灵敏度为95.11%，特异性为96.23%。
本研究呈现了不同MTB感染状态下中性粒细胞的全面蛋白质组概况，这种三种蛋白质组合可能有助于MTB感染的诊断。
本研究得到了中国医学科学院（CAMS）医学科学创新基金（2021-I2M-1-037）和中国国家科技重大专项（20212017ZX10201301-002-003）的支持。
