GSE193979
Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment
Globally, the anti-tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success rates are lower among people with diabetes mellitus (DM). Predicting treatment failure early after diagnosis would allow early treatment adaptation and may improve global TB control.  Methods  Samples were collected in a longitudinal cohort study of adult TB patients with or without concomitant DM from South Africa and Indonesia to characterize whole blood transcriptional profiles before and during anti-TB treatment, using unbiased RNA-Seq and targeted gene dcRT-MLPA.  Findings  We report differences in whole blood transcriptome profiles between patients with a good versus poor anti-TB treatment outcome, which were observed before initiation of treatment and throughout treatment. An eight-gene and 22-gene blood transcriptional signatures distinguished patients with a good treatment outcome from patients with a poor treatment outcome at diagnosis (AUC=0·815) or two weeks (AUC=0·834) after initiation of anti-TB treatment, respectively. Importantly, high accuracy was obtained by cross-validating this signature in an external cohort (AUC=0·749).  Interpretation  These findings suggest that transcriptional profiles can be used as a prognostic biomarker for treatment failure and success, even in patients with concomitant DM. Overall design: Whole blood was collected from patients with TB-only, TB-DM throughout anti tuberculosis treatment at four time points: Diagnosis, Week 2, Month 2 and Month 6 from two field sites; South Africa and Indonesia. Treatment outcome data were collected at Month 12