Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt


  • John Espen Gjøen
  • Synne Jenum
  • Dhanasekaran Sivakumaran
  • Aparna Mukherjee
  • Ragini Macaden
  • Sushil K Kabra
  • Rakesh Lodha
  • Tom H M Ottenhoff
  • Mariëlle C Haks
  • Timothy Mark Doherty
  • Ritz, Christian
  • Harleen M S Grewal

Pediatric tuberculosis (TB) is challenging to diagnose, confirmed by growth of Mycobacterium tuberculosis at best in 40% of cases. The WHO has assigned high priority to the development of non-sputum diagnostic tools. We therefore sought to identify transcriptional signatures in whole blood of Indian children, capable of discriminating intra-thoracic TB disease from other symptomatic illnesses. We investigated the expression of 198 genes in a training set, comprising 47 TB cases (19 definite/28 probable) and 36 asymptomatic household controls, and identified a 7- and a 10-transcript signature, both including NOD2, GBP5, IFITM1/3, KIF1B and TNIP1. The discriminatory abilities of the signatures were evaluated in a test set comprising 24 TB cases (17 definite/7 probable) and 26 symptomatic non-TB cases. In separating TB-cases from symptomatic non-TB cases, both signatures provided an AUC of 0.94 (95%CI, 0.88-1.00), a sensitivity of 91.7% (95%CI, 71.5-98.5) regardless of culture status, and 100% sensitivity for definite TB. The 7-transcript signature provided a specificity of 80.8% (95%CI, 60.0-92.7), and the 10-transcript signature a specificity of 88.5% (95%CI, 68.7-96.9%). Although warranting exploration and validation in other populations, our findings are promising and potentially relevant for future non-sputum based POC diagnostic tools for pediatric TB.

TidsskriftScientific Reports
Antal sider9
StatusUdgivet - 2017

Bibliografisk note

CURIS 2017 NEXS 198

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