Shuibao Xu, Renfang Zhang, Li Liu, Jun Chen, Zhenyan Wang, Tangkai Qi, Jianjun Sun, Wei Song, Yang Tang, Junyang Yang, Youming Chen, Yueming Shao, Jingna Xun, Xinyu Zhang, Zichen Song, Yinzhong Shen, Hongzhou Lu
This study evaluates the potential of plasma extracellular vesicle (EV)-associated miRNAs as diagnostic and differential-diagnostic biomarkers to distinguish tuberculosis (TB) from non-tuberculous mycobacterial infection (NTM) among AIDS patients. A cohort of 125 AIDS patients admitted to the Infectious Diseases and Immunology Department of Shanghai Public Health Clinical Center from January 2021 to January 2024 was categorized into AIDS/TB, AIDS/NTM, and AIDS control groups; in the discovery phase, 15 cases (AIDS/TB: 3, AIDS/NTM: 9, AIDS controls: 3) were used to isolate plasma-derived EVs and perform high-throughput sequencing to construct miRNA expression profiles, followed by validation in a large-sample cohort of 110 cases using qPCR. Diagnostic and differential diagnostic value were evaluated with ROC curves, area under the curve (AUC), and the Youden index. In the discovery phase, differentially expressed EV-associated miRNAs were observed among the three groups and among different NTM species; miR-374a-5p and miR-652-3p were markedly downregulated in AIDS/NTM versus AIDS/TB and AIDS controls, while let-7c-5p was upregulated in both AIDS/NTM and AIDS/TB versus AIDS controls. In the validation phase (n=110), miR-374a-5p showed no significant difference between AIDS/TB and AIDS controls but was lower in AIDS/NTM; miR-652-3p was higher in AIDS/TB than controls and lower in AIDS/NTM than controls and AIDS/TB; let-7c-5p was significantly higher in both AIDS/TB and AIDS/NTM than controls, with AIDS/NTM higher than AIDS/TB. ROC analyses yielded: AIDS control vs AIDS/NTM-miR-374a-5p AUC 0.7263, miR-652-3p AUC 0.9947, let-7c-5p AUC 1.0000; AIDS control vs AIDS/TB-miR-374a-5p AUC 0.6800, miR-652-3p AUC 0.7900, let-7c-5p AUC 1.0000; AIDS/NTM vs AIDS/TB-miR-374a-5p AUC 0.8220, miR-652-3p AUC 0.9993, let-7c-5p AUC 0.6613. Collectively, plasma EV-associated miR-374a-5p, miR-652-3p, and let-7c-5p show potential as diagnostic and differential-diagnostic biomarkers for distinguishing TB from NTM infections in AIDS patients, offering a prospective direction for TB/NTM diagnostic strategies in this population.