Abstract:
Methods: We developed a parsimonious PCR-based host-blood transcriptomic signature, RISK6, comprising three upregulated genes (GBP2, FCGR1B, SERPING1) and three downregulated genes (TUBGCP6, TRMT2A, SDR39U1). Utility was validated through quantitative real-time PCR in seven independent cohorts across South Africa, Ethiopia, The Gambia, Peru, and Brazil.
Results: RISK6 prognostic performance exceeded previous signatures in the same cohort (AUC 87.6% within 12 months of diagnosis). For diagnosing clinical disease, performance exceeded 85% in both HIV-infected and uninfected individuals. Scores correlated significantly with metabolic lung lesion activity (measured by PET-CT) and tracked treatment response, decreasing during successful therapy. Performance in capillary blood from finger-pricks was noninferior to venous blood.
Conclusion: RISK6 is a robust tool for identifying individuals at risk of incident disease, screening for tuberculosis, and monitoring treatment response. Its effectiveness in small capillary blood volumes supports its translation into rapid, point-of-care PCR devices.
Keywords: tuberculosis, IGRA, QuantiFERON-Plus, LTBI, screening, quality control.
Clique aqui
- Data de Publicação: 25/05/2020
- Autores: Adam Penn-Nicholson1,34, Stanley Kimbung Mbandi 1,34, EthanThompson2,34, Simon C. Mendelsohn 1,34, Sara Suliman 1,3, Novel N. Chegou4, StephanusT. Malherbe4, Fatoumatta Darboe 1, Mzwandile Erasmus1, WillemA. Hanekom1, Nicole Bilek1, Michelle Fisher1, Stefan H. E. Kaufmann5,6, JillWinter7, Melissa Murphy1, RobinWood8, Carl Morrow8, IldikoVan Rhijn3, Branch Moody3, Megan Murray9, Bruno B.Andrade 10, Timothy R. Sterling11, Jayne Sutherland12, Kogieleum Naidoo13,14, Nesri Padayatchi13,14, GerhardWalzl 4, Mark Hatherill 1, Daniel Zak2, Thomas J. Scriba 1 ✉, 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* & The CAPRISA IMPRESS team*
