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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085486/ https://www.ncbi.nlm.nih.gov/pubmed/33936077 http://dx.doi.org/10.3389/fimmu.2021.653898 |
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author | Kumar, Nathella Pavan Hissar, Syed Thiruvengadam, Kannan Banurekha, Velayuthum V. Suresh, N. Shankar, Janani S, Elilarasi N S, Gomathi S, Kalpana J, Ganesh M A, Aravind Baskaran, Dhanaraj Tripathy, Srikanth Swaminathan, Soumya Babu, Subash |
author_facet | Kumar, Nathella Pavan Hissar, Syed Thiruvengadam, Kannan Banurekha, Velayuthum V. Suresh, N. Shankar, Janani S, Elilarasi N S, Gomathi S, Kalpana J, Ganesh M A, Aravind Baskaran, Dhanaraj Tripathy, Srikanth Swaminathan, Soumya Babu, Subash |
author_sort | Kumar, Nathella Pavan |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8085486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80854862021-05-01 Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis Kumar, Nathella Pavan Hissar, Syed Thiruvengadam, Kannan Banurekha, Velayuthum V. Suresh, N. Shankar, Janani S, Elilarasi N S, Gomathi S, Kalpana J, Ganesh M A, Aravind Baskaran, Dhanaraj Tripathy, Srikanth Swaminathan, Soumya Babu, Subash Front Immunol Immunology 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. Frontiers Media S.A. 2021-04-16 /pmc/articles/PMC8085486/ /pubmed/33936077 http://dx.doi.org/10.3389/fimmu.2021.653898 Text en Copyright © 2021 Kumar, Hissar, Thiruvengadam, Banurekha, Suresh, Shankar, S, N S, S, J, M A, Baskaran, Tripathy, Swaminathan and Babu https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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. |
spellingShingle | Immunology Kumar, Nathella Pavan Hissar, Syed Thiruvengadam, Kannan Banurekha, Velayuthum V. Suresh, N. Shankar, Janani S, Elilarasi N S, Gomathi S, Kalpana J, Ganesh M A, Aravind Baskaran, Dhanaraj Tripathy, Srikanth Swaminathan, Soumya Babu, Subash Discovery and Validation of a Three-Cytokine Plasma Signature as a Biomarker for Diagnosis of Pediatric Tuberculosis |
title | 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_short | 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 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085486/ https://www.ncbi.nlm.nih.gov/pubmed/33936077 http://dx.doi.org/10.3389/fimmu.2021.653898 |
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