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结核病患者家庭接触者的QuantiFERON上清液中预测进展为活动性结核病风险的代谢物特征。

Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients.

作者信息

Daniel Evangeline Ann, Upadhyay Shubham, Selvachithiram Murugesan, Pattabiraman Sathyamurthi, Bhanu Brindha, Sivaprakasam Amsaveni, Kulkarni Vandana, Karyakarte Rajesh, Gaikwad Sanjay, Paradkar Mandar, Yogendra Shivakumar Shri Vijay Bala, Mave Vidya, Gupta Amita, Prasad Keshava, Hanna Luke Elizabeth

机构信息

Department of Virology and Biotechnology, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, India.

University of Madras, Chennai, India.

出版信息

Emerg Microbes Infect. 2025 Dec;14(1):2437242. doi: 10.1080/22221751.2024.2437242. Epub 2024 Dec 22.

DOI:10.1080/22221751.2024.2437242
PMID:39628384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11703509/
Abstract

The identification of individuals with the greatest risk of progression to active tuberculosis (TB) disease from the huge reservoir of () infected individuals continues to remain an arduous ascent in the global effort to control TB. In a two-year prospective study, we analysed metabolic profiles in the unstimulated and TB antigen stimulated QuantiFERON supernatants of 14 healthy household contacts (HHCs) who progressed to TB disease (Progressors) and 14 HHCs who remained healthy (Non-Progressors). We identified 21 significantly dysregulated metabolites in the TB antigen-stimulated QuantiFERON supernatants of Progressors, of which the combination of Malic acid and N-Arachidonoylglycine had maximum AUC of 0.99. Eighteen significantly dysregulated metabolites were identified in the unstimulated QuantiFERON supernatants of Progressors, among which the combination of Orotic acid and the phosphatidylcholines PC (O-34:1), PC (O-18:1(9Z)/16:0), PC (O-18:1(11Z)/16:0) had the maximum AUC of 0.98. Most of the dysregulated metabolites belonged to the pathways of fatty acid metabolism, lipid metabolism and nitric oxide metabolism. Validation of these metabolic signatures in large, diverse cohorts would pave way for the development of a robust test that can identify individuals at high risk of TB for targetted intervention of TB disease.

摘要

在全球结核病防控工作中，从大量潜伏感染个体中识别出进展为活动性结核病风险最高的个体仍然是一项艰巨的任务。在一项为期两年的前瞻性研究中，我们分析了14名进展为结核病的健康家庭接触者（进展者）和14名保持健康的健康家庭接触者（非进展者）在未刺激和经结核抗原刺激的全血γ-干扰素释放试验上清液中的代谢谱。我们在进展者经结核抗原刺激的全血γ-干扰素释放试验上清液中鉴定出21种显著失调的代谢物，其中苹果酸和N-花生四烯酰甘氨酸的组合曲线下面积最大，为0.99。在进展者未刺激的全血γ-干扰素释放试验上清液中鉴定出18种显著失调的代谢物，其中乳清酸与磷脂酰胆碱PC（O-34:1）、PC（O-18:1(9Z)/16:0）、PC（O-18:1(11Z)/16:0）的组合曲线下面积最大，为0.98。大多数失调的代谢物属于脂肪酸代谢、脂质代谢和一氧化氮代谢途径。在大型、多样化队列中验证这些代谢特征将为开发一种强大的检测方法铺平道路，该方法可以识别结核病高风险个体，以便对结核病进行针对性干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/684c697db2cc/TEMI_A_2437242_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/c494eab296ed/TEMI_A_2437242_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/fbe88c3d620b/TEMI_A_2437242_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/9753e9a19913/TEMI_A_2437242_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/684c697db2cc/TEMI_A_2437242_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/c494eab296ed/TEMI_A_2437242_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/fbe88c3d620b/TEMI_A_2437242_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/9753e9a19913/TEMI_A_2437242_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0185/11703509/684c697db2cc/TEMI_A_2437242_F0004_OC.jpg

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