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 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 a...

Full description

Saved in:
Bibliographic Details
Main Authors: Evangeline Ann Daniel, Shubham Upadhyay, Murugesan Selvachithiram, Sathyamurthi Pattabiraman, Brindha Bhanu, Amsaveni Sivaprakasam, Vandana Kulkarni, Rajesh Karyakarte, Sanjay Gaikwad, Mandar Paradkar, Shri Vijay Bala Yogendra Shivakumar, Vidya Mave, Amita Gupta, Keshava Prasad, Luke Elizabeth Hanna
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2024.2437242
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846111719180468224
author Evangeline Ann Daniel
Shubham Upadhyay
Murugesan Selvachithiram
Sathyamurthi Pattabiraman
Brindha Bhanu
Amsaveni Sivaprakasam
Vandana Kulkarni
Rajesh Karyakarte
Sanjay Gaikwad
Mandar Paradkar
Shri Vijay Bala Yogendra Shivakumar
Vidya Mave
Amita Gupta
Keshava Prasad
Luke Elizabeth Hanna
author_facet Evangeline Ann Daniel
Shubham Upadhyay
Murugesan Selvachithiram
Sathyamurthi Pattabiraman
Brindha Bhanu
Amsaveni Sivaprakasam
Vandana Kulkarni
Rajesh Karyakarte
Sanjay Gaikwad
Mandar Paradkar
Shri Vijay Bala Yogendra Shivakumar
Vidya Mave
Amita Gupta
Keshava Prasad
Luke Elizabeth Hanna
author_sort Evangeline Ann Daniel
collection DOAJ
description 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.
format Article
id doaj-art-ccd573d0a8984703b210dbfe4055f65d
institution Kabale University
issn 2222-1751
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
record_format Article
series Emerging Microbes and Infections
spelling doaj-art-ccd573d0a8984703b210dbfe4055f65d2024-12-23T06:57:57ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2024.2437242Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patientsEvangeline Ann Daniel0Shubham Upadhyay1Murugesan Selvachithiram2Sathyamurthi Pattabiraman3Brindha Bhanu4Amsaveni Sivaprakasam5Vandana Kulkarni6Rajesh Karyakarte7Sanjay Gaikwad8Mandar Paradkar9Shri Vijay Bala Yogendra Shivakumar10Vidya Mave11Amita Gupta12Keshava Prasad13Luke Elizabeth Hanna14Department of Virology and Biotechnology, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, IndiaCenter for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, IndiaDepartment of Virology and Biotechnology, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, IndiaDepartment of Virology and Biotechnology, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, IndiaDepartment of Virology and Biotechnology, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, IndiaDepartment of Virology and Biotechnology, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, IndiaBJ Government Medical College-Johns Hopkins Clinical Research Site, Pune, IndiaByramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, IndiaByramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, IndiaJohns Hopkins Center for Infectious Diseases in India, Pune, IndiaJohns Hopkins Center for Infectious Diseases in India, Pune, IndiaJohns Hopkins Center for Infectious Diseases in India, Pune, IndiaJohns Hopkins University School of Medicine, Baltimore, MD, USACenter for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, IndiaDepartment of Virology and Biotechnology, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR), Chennai, IndiaThe 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.https://www.tandfonline.com/doi/10.1080/22221751.2024.2437242MetabolitestuberculosisprogressionQuantiFERON supernatantbiomarkersmetabolite signatures
spellingShingle Evangeline Ann Daniel
Shubham Upadhyay
Murugesan Selvachithiram
Sathyamurthi Pattabiraman
Brindha Bhanu
Amsaveni Sivaprakasam
Vandana Kulkarni
Rajesh Karyakarte
Sanjay Gaikwad
Mandar Paradkar
Shri Vijay Bala Yogendra Shivakumar
Vidya Mave
Amita Gupta
Keshava Prasad
Luke Elizabeth Hanna
Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients
Emerging Microbes and Infections
Metabolites
tuberculosis
progression
QuantiFERON supernatant
biomarkers
metabolite signatures
title Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients
title_full Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients
title_fullStr Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients
title_full_unstemmed Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients
title_short Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients
title_sort predictive metabolite signatures for risk of progression to active tb from quantiferon supernatants of household contacts of tb patients
topic Metabolites
tuberculosis
progression
QuantiFERON supernatant
biomarkers
metabolite signatures
url https://www.tandfonline.com/doi/10.1080/22221751.2024.2437242
work_keys_str_mv AT evangelineanndaniel predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT shubhamupadhyay predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT murugesanselvachithiram predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT sathyamurthipattabiraman predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT brindhabhanu predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT amsavenisivaprakasam predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT vandanakulkarni predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT rajeshkaryakarte predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT sanjaygaikwad predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT mandarparadkar predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT shrivijaybalayogendrashivakumar predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT vidyamave predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT amitagupta predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT keshavaprasad predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients
AT lukeelizabethhanna predictivemetabolitesignaturesforriskofprogressiontoactivetbfromquantiferonsupernatantsofhouseholdcontactsoftbpatients