Background:
The World Health Organization’s End TB Strategy requires new tools to identify individuals at high risk of progressing from Mycobacterium tuberculosis infection to active disease. While several host-blood transcriptomic signatures have been developed, their large number of genes makes them difficult to implement in resource-limited settings. There is an urgent need for simpler, parsimonious biomarkers that can be easily translated into point-of-care diagnostic platforms.
Abstract:
Methods: We developed a 2-gene transcriptomic signature (Silveira-Mattos-2 or SM2) using RNA-sequencing data from a South African adolescent cohort. The signature, consisting of the ratio of GBP5 and KIF1B expression, was validated using quantitative RT-PCR in independent cohorts from South Africa, Ethiopia, The Gambia, and Brazil (RePORT-Brazil).
Results: The SM2 signature significantly discriminated between progressors and non-progressors up to two years before TB diagnosis. In the validation cohorts, its prognostic performance (AUC 0.70 within 12 months of diagnosis) was equivalent to more complex signatures like the ACS 16-gene signature. In the Brazilian cohort, the signature also showed high accuracy in identifying active TB cases compared to healthy contacts.
Conclusion: The SM2 signature provides a robust and simplified approach for predicting TB progression. Due to its parsimonious nature (requiring only two genes), it is an ideal candidate for further development into inexpensive, PCR-based point-of-care tests in high-burden countries.
Keywords: Tuberculosis; Latent infection; Biomarkers; Transcriptome; Prognosis; PCR.
Clique aqui
- Data de Publicação: 27/11/2019
- Autores: Yukari C. Manabe1 , Bruno B. Andrade2,3,4 , Nikhil Gupte1,5 , Samantha Leong6 , Manisha Kintali6 , Mitch Matoga7 , Cynthia Riviere8 , Wadzanai Sameneka9 , Javier R. Lama10 , Kogieleum Naidoo11,12, Yue Zhao13, W. Evan Johnson13, Jerrold J. Ellner6 , Mina C. Hosseinipour7,14, Gregory P. Bisson15, Padmini Salgame6 , Amita Gupta1 for the ACTG A5274 REMEMBER and NWCS 408 Study Team
