Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum

The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is like...

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Main Authors:	Jenum, Synne, Dhanasekaran, S., Lodha, Rakesh, Mukherjee, Aparna, Kumar Saini, Deepak, Singh, Sarman, Singh, Varinder, Medigeshi, Guruprasad, Haks, Marielle C., Ottenhoff, Tom H. M., Doherty, Timothy Mark, Kabra, Sushil K., Ritz, Christian, Grewal, Harleen M. S.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698754/

id	pubmed-4698754
recordtype	oai_dc
spelling	pubmed-46987542016-01-13 Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum Jenum, Synne Dhanasekaran, S. Lodha, Rakesh Mukherjee, Aparna Kumar Saini, Deepak Singh, Sarman Singh, Varinder Medigeshi, Guruprasad Haks, Marielle C. Ottenhoff, Tom H. M. Doherty, Timothy Mark Kabra, Sushil K. Ritz, Christian Grewal, Harleen M. S. Article The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%). Nature Publishing Group 2016-01-04 /pmc/articles/PMC4698754/ /pubmed/26725873 http://dx.doi.org/10.1038/srep18520 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Jenum, Synne Dhanasekaran, S. Lodha, Rakesh Mukherjee, Aparna Kumar Saini, Deepak Singh, Sarman Singh, Varinder Medigeshi, Guruprasad Haks, Marielle C. Ottenhoff, Tom H. M. Doherty, Timothy Mark Kabra, Sushil K. Ritz, Christian Grewal, Harleen M. S.
spellingShingle	Jenum, Synne Dhanasekaran, S. Lodha, Rakesh Mukherjee, Aparna Kumar Saini, Deepak Singh, Sarman Singh, Varinder Medigeshi, Guruprasad Haks, Marielle C. Ottenhoff, Tom H. M. Doherty, Timothy Mark Kabra, Sushil K. Ritz, Christian Grewal, Harleen M. S. Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
author_facet	Jenum, Synne Dhanasekaran, S. Lodha, Rakesh Mukherjee, Aparna Kumar Saini, Deepak Singh, Sarman Singh, Varinder Medigeshi, Guruprasad Haks, Marielle C. Ottenhoff, Tom H. M. Doherty, Timothy Mark Kabra, Sushil K. Ritz, Christian Grewal, Harleen M. S.
author_sort	Jenum, Synne
title	Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
title_short	Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
title_full	Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
title_fullStr	Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
title_full_unstemmed	Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
title_sort	approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum
description	The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698754/
_version_	1613519109329256448

Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum

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