RGD Reference Report - Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum. - Rat Genome Database

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

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 
Citation: Jenum S, etal., Sci Rep. 2016 Jan 4;6:18520. doi: 10.1038/srep18520.
RGD ID: 124715450
Pubmed: PMID:26725873   (View Abstract at PubMed)
PMCID: PMC4698754   (View Article at PubMed Central)
DOI: DOI:10.1038/srep18520   (Journal Full-text)

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%).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tuberculosis susceptibilityHEP 124715450mRNA:decreased expression:blood (human)RGD 

Objects Annotated

Genes (Homo sapiens)
CD8A  (CD8 subunit alpha)


Additional Information