The identification of individuals with the greatest risk of progression to active tuberculosis (TB) disease from the huge reservoir of Mycobacterium tuberculosis (Mtb) 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.

中文翻译：

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来自 TB 患者家庭接触者的 QuantiFERON 上清液中进展为活动性 TB 风险的预测代谢物特征。


从巨大的结核分枝杆菌 （Mtb） 感染个体库中识别出进展为活动性结核病 （TB） 风险最大的个体，仍然是全球控制结核病努力的艰巨任务。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 （HHC） 和 14 名保持健康的 HHC（非进展者）的未刺激和 TB 抗原刺激的 QuantiFERON 上清液中的代谢特征。我们在 Progressors 的 TB 抗原刺激的 QuantiFERON 上清液中鉴定了 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的最大 AUC 为 0.99。在 Progressors 的未刺激 QuantiFERON 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） 的组合最大 AUC 为 0.98。失调的代谢产物大多属于脂肪酸代谢、脂质代谢和一氧化氮代谢途径。在大型、不同的队列中验证这些代谢特征将为开发一种强大的测试铺平道路，该测试可以识别结核病高危个体以进行结核病的针对性干预。