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

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...

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Bibliographic Details
Published in:Emerging microbes & infections 2025-12, Vol.14 (1), p.2437242
Main Authors: 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
Format: Article
Language:English
Subjects:
Adult
biomarkers
Disease Progression
Family Characteristics
Female
Humans
Interferon-gamma Release Tests - methods
Male
metabolite signatures
Metabolites
Metabolome
Middle Aged
Mycobacterium tuberculosis - immunology
progression
Prospective Studies
QuantiFERON supernatant
tuberculosis
Tuberculosis - diagnosis
Young Adult
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Summary: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.
ISSN:2222-1751
2222-1751
DOI:10.1080/22221751.2024.2437242