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

Synne Jenum; S Dhanasekaran; Rakesh Lodha; Aparna Mukherjee; Deepak Kumar Saini; Sarman Singh; Varinder Singh; Guruprasad Medigeshi; Marielle C Haks; Tom H M Ottenhoff; Timothy Mark Doherty; Sushil K Kabra; Christian Ritz; Harleen M S Grewal

doi:10.1038/srep18520

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

Synne Jenum, S Dhanasekaran, Rakesh Lodha, Aparna Mukherjee, Deepak Kumar Saini, Sarman Singh, Varinder Singh, Guruprasad Medigeshi, Marielle C Haks, Tom H M Ottenhoff, Timothy Mark Doherty, Sushil K Kabra, Christian Ritz, Harleen M S Grewal

Lifecourse Nutrition & Health

19 Citations (Scopus)

Abstract

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%).

Original language	English
Article number	18520
Journal	Scientific Reports
Volume	6
Number of pages	11
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep18520
Publication status	Published - 4 Jan 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/srep18520

srep18520.pdfFinal published version, 2.22 MBLicence: CC BY

Cite this

Jenum, S., Dhanasekaran, S., Lodha, R., Mukherjee, A., Kumar Saini, D., Singh, S., Singh, V., Medigeshi, G., Haks, M. C., Ottenhoff, T. H. M., Doherty, T. M., Kabra, S. K., Ritz, C., & Grewal, H. M. S. (2016). Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum. Scientific Reports, 6, [18520]. https://doi.org/10.1038/srep18520

Jenum, S, Dhanasekaran, S, Lodha, R, Mukherjee, A, Kumar Saini, D, Singh, S, Singh, V, Medigeshi, G, Haks, MC, Ottenhoff, THM, Doherty, TM, Kabra, SK, Ritz, C & Grewal, HMS 2016, 'Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum', Scientific Reports, vol. 6, 18520. https://doi.org/10.1038/srep18520

@article{8c0b31c84b5c4f128460ee28890b3613,

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

abstract = "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%).",

author = "Synne Jenum and S Dhanasekaran and Rakesh Lodha and Aparna Mukherjee and {Kumar Saini}, Deepak and Sarman Singh and Varinder Singh and Guruprasad Medigeshi and Haks, {Marielle C} and Ottenhoff, {Tom H M} and Doherty, {Timothy Mark} and Kabra, {Sushil K} and Christian Ritz and Grewal, {Harleen M S}",

note = "CURIS 2016 NEXS 020",

year = "2016",

month = jan,

day = "4",

doi = "10.1038/srep18520",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "nature publishing group",

}

TY - JOUR

T1 - Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum

AU - Jenum, Synne

AU - Dhanasekaran, S

AU - Lodha, Rakesh

AU - Mukherjee, Aparna

AU - Kumar Saini, Deepak

AU - Singh, Sarman

AU - Singh, Varinder

AU - Medigeshi, Guruprasad

AU - Haks, Marielle C

AU - Ottenhoff, Tom H M

AU - Doherty, Timothy Mark

AU - Kabra, Sushil K

AU - Ritz, Christian

AU - Grewal, Harleen M S

N1 - CURIS 2016 NEXS 020

PY - 2016/1/4

Y1 - 2016/1/4

N2 - 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%).

AB - 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%).

U2 - 10.1038/srep18520

DO - 10.1038/srep18520

M3 - Journal article

C2 - 26725873

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 18520

ER -

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

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this