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Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

Article scientifique 2022 Anglais

Résumé

Abstract Background 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 is 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, which were observed before initiation of treatment and throughout treatment, between patients with a good versus poor anti- TB treatment outcome. An eight-gene and a 22-gene blood transcriptional signature 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. 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. Funding The research leading to these results, as part of the TANDEM Consortium, received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013 Grant Agreement No. 305279) and the Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038).

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Doorn, C., Eckold, C., Ronacher, K., Ruslami, R., Veen, S., Lee, J., Kumar, V., Kerry‐Barnard, S., Malherbe, S., Kleynhans, L., Stanley, K., Hill, P., Joosten, S., Crevel, R., Wijmenga, C., Critchley, J., Walzl, G., Alisjahbana, B., Haks, M., Dockrell, H., Ottenhoff, T., Vianello, E., Cliff, J. (2022). Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment. https://doi.org/10.1101/2022.02.08.22269796

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Auteur(s)

Cassandra L. R. van Doorn Clare Eckold Katharina Ronacher Rovina Ruslami Suzanne van Veen Ji‐Sook Lee Vinod Kumar Sarah Kerry‐Barnard Stephanus T. Malherbe Léanie Kleynhans Kim Stanley Philip C. Hill Simone A. Joosten Reinout van Crevel Cisca Wijmenga Julia Critchley Gerhard Walzl Bachti Alisjahbana Mariëlle C. Haks Hazel M. Dockrell Tom H. M. Ottenhoff Eleonora Vianello Jacqueline M. Cliff

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