RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response

Penn-Nicholson, A. et al. (2020) RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response. Scientific Reports, 10, 8629. (doi: 10.1038/s41598-020-65043-8) (PMID:32451443) (PMCID:PMC7248089)

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Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies.

Item Type:Articles
Additional Information:Amelia C. Crampin is a member of The GC6-74 Consortium and The AE-TBC Consortium.
Glasgow Author(s) Enlighten ID:Crampin, Professor Mia
Authors: Penn-Nicholson, A., Mbandi, S. K., Thompson, E., Mendelsohn, S. C., Suliman, S., Chegou, N. N., Malherbe, S. T., Darboe, F., Erasmus, M., Hanekom, W. A., Bilek, N., Fisher, M., Kaufmann, S. H. E., Winter, J., Murphy, M., Wood, R., Morrow, C., Van Rhijn, I., Moody, B., Murray, M., Andrade, B. B., Sterling, T. R., Sutherland, J., Naidoo, K., Padayatchi, N., Walzl, G., Hatherill, M., Zak, D., Scriba, T. J., The Adolescent Cohort Study team, , The GC6-74 Consortium, , The SATVI Clinical and Laboratory Team, , The ScreenTB Consortium, , The AE-TBC Consortium, , The RePORT Brazil Team, , Peruvian Household Contacts Cohort Team, , and The CAPRISA IMPRESS team,
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Scientific Reports 10: 8629
Publisher Policy:Reproduced under a Creative Commons License

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