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ORIGINAL RESEARCH article

Front. Tuberc
Sec. Diagnosis of Tuberculosis
Volume 2 - 2024 | doi: 10.3389/ftubr.2024.1415346
This article is part of the Research Topic Discerning active TB from latent infection View all articles

Discovery of a Circulating miRNA Signature that can Predict Onset of Active Tuberculosis among Household Contacts of Tuberculosis Patients

Provisionally accepted
Evangeline A. Daniel Evangeline A. Daniel 1,2Kannan Thiruvengadam Kannan Thiruvengadam 1Padmapriyadarsini Chandrasekaran Padmapriyadarsini Chandrasekaran 1Nancy Hilda Nancy Hilda 1Pavithra Umashankar Pavithra Umashankar 1Pooja Prashanthi Pooja Prashanthi 1Murugesan Selvachithiram Murugesan Selvachithiram 1Pattabiraman Sathyamurthi Pattabiraman Sathyamurthi 1Brindha Bhanu Brindha Bhanu 1Amsaveni Sivaprakasam Amsaveni Sivaprakasam 1Mandar Paradkar Mandar Paradkar 3,4Vandana Kulkarni Vandana Kulkarni 3,4Rajesh Karyakarte Rajesh Karyakarte 5Shri Vijay Bala Yogendra Shivakumar Shri Vijay Bala Yogendra Shivakumar 4Vidya Mave Vidya Mave 3,4,6Amita Gupta Amita Gupta 6Luke Elizabeth Hanna Luke Elizabeth Hanna 1*
  • 1 National Institute of Research in Tuberculosis (ICMR), Chennai, India
  • 2 University of Madras, Chennai, Tamil Nadu, India
  • 3 Johns Hopkins University Clinical Research Site, Byramjee-Jeejeebhoy Government Medical College, Pune, Maharashtra, India
  • 4 Center for Infectious Diseases in India (CIDI), Pune, Maharashtra, India
  • 5 B. J. Medical College & Sassoon Hospital, Pune, Maharashtra, India
  • 6 Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States

The final, formatted version of the article will be published soon.

    Non-sputum based predictive biomarkers capable of identifying individuals with high risk of progression to active tuberculosis (TB) are critical for global TB control. MicroRNAs (miRNAs) are significant regulators involved in TB pathogenesis and hence we aimed to identify a miRNA signature capable of predicting progression to TB disease.We compared the differential miRNA expression profile of QuantiFERON supernatants of TB Progressors, defined as healthy household contacts (HHCs) of TB patients, who developed active TB disease during a two-year follow-up period, and Non-progressors defined as HHCs from the same longitudinal cohort who did not develop TB disease during the entire follow-up period, using the nanostring nCounter platform. Receiver Operator Characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the identified miRNA biomarkers, followed by random forest analysis to determine the best predictive model.We identified 30 differentially regulated miRNAs between the two groups. Of these, hsa-miR-585-3p and hsa-miR-92a-3p were up-regulated with a maximum fold change of 1.74 and 1.71 respectively, while hsa-miR-223-3p and hsa-miR-451a were down-regulated by -2.05 and -2.04 fold respectively. Random forest analysis revealed that hsa-miR-181a-5p, hsa-miR-204-5p, hsa-miR-197-3p, hsa-miR-92a-3p, hsa-miR-451a, hsa-miR-24-3p and hsa-miR-487a-3p exhibited 100% accuracy in identifying Progressors. This panel of 7 miRNAs demonstrated excellent diagnostic performance characteristics with 100% sensitivity and specificity.We propose that the identified miRNA signature has the potential to serve as a very useful tool for early identification of individuals who bear the highest risk of progression to TB, so that they can be targeted for timely intervention.

    Keywords: miRNA, Tuberculosis, progression, QuantiFERON supernatant, biomarker

    Received: 10 Apr 2024; Accepted: 08 Oct 2024.

    Copyright: © 2024 Daniel, Thiruvengadam, Chandrasekaran, Hilda, Umashankar, Prashanthi, Selvachithiram, Sathyamurthi, Bhanu, Sivaprakasam, Paradkar, Kulkarni, Karyakarte, Shivakumar, Mave, Gupta and Hanna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Luke Elizabeth Hanna, National Institute of Research in Tuberculosis (ICMR), Chennai, India

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