Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783686350473527296
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
work_keys_str_mv AT kumarnathellapavan discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT hissarsyed discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT thiruvengadamkannan discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT banurekhavelayuthumv discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT sureshn discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT shankarjanani discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT selilarasi discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT nsgomathi discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT skalpana discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT jganesh discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT maaravind discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT baskarandhanaraj discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT tripathysrikanth discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT swaminathansoumya discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis
AT babusubash discoveryandvalidationofathreecytokineplasmasignatureasabiomarkerfordiagnosisofpediatrictuberculosis