Kinetics of whole blood transcriptional responses during progression from infection to TB disease.

<p>(A) Consort diagram showing participant selection of the progressor and control substudy from the Adolescent Cohort Study (ACS). A total of 6,363 adolescents (12–18 years of age) were enrolled into the ACS. Participants were stratified according to their baseline <i>M</i>.<i>tb-</i>infection status according to either QFT-positive (≥0.35 IU/ml) and/or TST induration ≥ 10mm. Individuals with unknown QFT and TST test results were excluded. Participants with baseline <i>M</i>.<i>tb</i>-infection or who were QFT-negative and TST-negative at baseline but converted their tests at a later time point were eligible for inclusion as progressors or controls. Progressors developed intrathoracic TB disease, defined as TB diagnosis by at least two consecutive sputum smear positive tests, or at least one microbiologically confirmed culture positive test, at least 6 months after detection of <i>M</i>.<i>tb-</i>infection. Progressors were matched to healthy <i>M</i>.<i>tb-</i>infected “controls” based on age, gender, ethnicity, school, and any prior history of TB disease at a ~1:2 ratio. (B) Genes found to be significantly up (red) or down (blue) regulated in progressors relative to controls, ranked according to the time to TB disease at which expression in progressors (n = 38) is significantly different to controls (n = 104) (see <b><a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006687#ppat.1006687.s001" target="_blank">S1 Fig</a></b>). The full list of significantly regulated genes is in <b><a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006687#ppat.1006687.s006" target="_blank">S2 Table</a></b>.