Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis
Pediatric TB poses challenge in diagnosis due to the paucibacillary nature of the disease. We conducted a prospective diagnostic study to identify immune biomarkers of pediatric TB and controls (discovery cohort) and obtained a separate “validation” cohort of confirmed cases of pediatric TB and cont...
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doaj-6a3d6b5a071d46cbb6a37a3201b7dff92021-04-16T05:24:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.653898653898Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric TuberculosisNathella Pavan Kumar0Nathella Pavan Kumar1Syed Hissar2Kannan Thiruvengadam3Velayuthum V. Banurekha4N. Suresh5Janani Shankar6Elilarasi S7Gomathi N S8Kalpana S9Ganesh J10Aravind M A11Dhanaraj Baskaran12Srikanth Tripathy13Soumya Swaminathan14Soumya Swaminathan15Subash Babu16Subash Babu17National Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaDepartment of Pediatrics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, IndiaDepartment of Pediatrics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, IndiaDepartment of Pediatrics, Institute of Child Health and Hospital for Children, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaDepartment of Pediatrics, Institute of Child Health and Hospital for Children, Chennai, IndiaDepartment of Pediatrics, Government Stanley Medical College and Hospital, Chennai, IndiaDepartment of Pediatrics, Government Stanley Medical College and Hospital, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaIndian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, IndiaPublic Health Division, World Health Organization, Geneva, SwitzerlandNational Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research, Chennai, IndiaLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, United StatesPediatric TB poses challenge in diagnosis due to the paucibacillary nature of the disease. We conducted a prospective diagnostic study to identify immune biomarkers of pediatric TB and controls (discovery cohort) and obtained a separate “validation” cohort of confirmed cases of pediatric TB and controls. Multiplex ELISA was performed to examine the plasma levels of cytokines. Discovery and validation cohorts revealed that baseline plasma levels of IFNγ, TNFα, IL-2, and IL-17A were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics (ROC) curve analysis revealed that IFNγ, IL-2, TNFα, and IL-17A (in the discovery cohort) and TNFα and IL-17A (in the validation cohort) could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 90%. In the discovery cohort, cytokines levels were significantly diminished following anti-tuberculosis treatment. In both the cohorts, combiROC models offered 100% sensitivity and 98% to 100% specificity for a three-cytokine signature of TNFα, IL-2, and IL-17A, which can distinguish confirmed or unconfirmed TB children from unlikely TB. Thus, a baseline cytokine signature of TNFα, IL-2, and IL-17A could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.653898/fullpediatric tuberculosiscytokinesbiomarkersELISAtuberculosis diagnosticsanti-tuberculosis treatment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nathella Pavan Kumar Nathella Pavan Kumar Syed Hissar Kannan Thiruvengadam Velayuthum V. Banurekha N. Suresh Janani Shankar Elilarasi S Gomathi N S Kalpana S Ganesh J Aravind M A Dhanaraj Baskaran Srikanth Tripathy Soumya Swaminathan Soumya Swaminathan Subash Babu Subash Babu |
spellingShingle |
Nathella Pavan Kumar Nathella Pavan Kumar Syed Hissar Kannan Thiruvengadam Velayuthum V. Banurekha N. Suresh Janani Shankar Elilarasi S Gomathi N S Kalpana S Ganesh J Aravind M A Dhanaraj Baskaran Srikanth Tripathy Soumya Swaminathan Soumya Swaminathan Subash Babu Subash Babu Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis Frontiers in Immunology pediatric tuberculosis cytokines biomarkers ELISA tuberculosis diagnostics anti-tuberculosis treatment |
author_facet |
Nathella Pavan Kumar Nathella Pavan Kumar Syed Hissar Kannan Thiruvengadam Velayuthum V. Banurekha N. Suresh Janani Shankar Elilarasi S Gomathi N S Kalpana S Ganesh J Aravind M A Dhanaraj Baskaran Srikanth Tripathy Soumya Swaminathan Soumya Swaminathan Subash Babu Subash Babu |
author_sort |
Nathella Pavan Kumar |
title |
Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis |
title_short |
Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis |
title_full |
Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis |
title_fullStr |
Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis |
title_full_unstemmed |
Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis |
title_sort |
discovery and validation of a three-cytokine plasma signature as a biomarker for diagnosis of pediatric tuberculosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-04-01 |
description |
Pediatric TB poses challenge in diagnosis due to the paucibacillary nature of the disease. We conducted a prospective diagnostic study to identify immune biomarkers of pediatric TB and controls (discovery cohort) and obtained a separate “validation” cohort of confirmed cases of pediatric TB and controls. Multiplex ELISA was performed to examine the plasma levels of cytokines. Discovery and validation cohorts revealed that baseline plasma levels of IFNγ, TNFα, IL-2, and IL-17A were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics (ROC) curve analysis revealed that IFNγ, IL-2, TNFα, and IL-17A (in the discovery cohort) and TNFα and IL-17A (in the validation cohort) could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 90%. In the discovery cohort, cytokines levels were significantly diminished following anti-tuberculosis treatment. In both the cohorts, combiROC models offered 100% sensitivity and 98% to 100% specificity for a three-cytokine signature of TNFα, IL-2, and IL-17A, which can distinguish confirmed or unconfirmed TB children from unlikely TB. Thus, a baseline cytokine signature of TNFα, IL-2, and IL-17A could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis. |
topic |
pediatric tuberculosis cytokines biomarkers ELISA tuberculosis diagnostics anti-tuberculosis treatment |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.653898/full |
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