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Learn MoreIdentification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease.; RESULTS:Between July 6, 2005, and April 23, 2007, we enrolled 6363 from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 661% (95% CI 632689) and a specificity of 806% (792820) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0018 for RNA sequencing and p=00095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <00001 by qRT-PCR) with a sensitivity of 537% (426643) and a specificity of 828% (76786) in 12 months preceding tuberculosis.; Interpretation: The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. SOURCE: Daniel Zak (daniel.zak@cidresearch.org) - Zak Lab Center for Infectious Disease Research
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