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Blood transcriptomic stratification of short-term risk in contacts of tuberculosis

Roe, J; Venturini, C; Gupta, R; Gurry, C; Chain, BM; Sun, Y; Southern, J; ... Noursadeghi, M; + view all (2019) Blood transcriptomic stratification of short-term risk in contacts of tuberculosis. Clinical Infectious Diseases 10.1093/cid/ciz252. (In press). Green open access

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Abstract

Background: The highest risk of tuberculosis (TB) arises in the first few months after exposure. We reasoned that this risk reflects incipient disease among TB contacts. Blood transcriptional biomarkers of TB may predate clinical diagnosis, suggesting they offer improved sensitivity to detect subclinical incipient disease. Therefore, we sought to test the hypothesis that refined blood transcriptional biomarkers of active TB will improve stratification of short-term disease risk in TB contacts. Methods: We combined analysis of previously published blood transcriptomic data with new data from a prospective HIV negative United Kingdom cohort of 333 TB contacts. We used stability selection as an alternative computational approach to identify an optimal signature for short-term risk of active TB, and evaluated its predictive value in independent cohorts. Results: In a previously published HIV negative South African casecontrol study of patients with asymptomatic Mycobacterium tuberculosis infection, a novel three-gene transcriptional signature comprising BATF2, GBP5 and SCARF1 achieved a positive predictive value (PPV) of 23% for progression to active TB within 90 days. In a new UK cohort of 333 HIV negative TB contacts with a median follow up of 346 days, this signature achieved a PPV of 50% (95% confidence interval: 15.7-84.3) and NPV of 99.3% (97.599.9). By comparison, peripheral blood interferon gamma release assays in the same cohort achieved a PPV of 5.6% (2.1-11.8). Conclusion: This blood transcriptional signature provides unprecedented opportunities to target therapy among TB contacts with greatest risk of incident disease.

Type: Article
Title: Blood transcriptomic stratification of short-term risk in contacts of tuberculosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/ciz252
Publisher version: http://doi.org/10.1093/cid/ciz252
Language: English
Additional information: Copyright © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Blood transcriptome; biomarker; tuberculosis; diagnosis.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10071382
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