A serum circulating miRNA signature for short-term risk of progression to active tuberculosis among household contacts

Duffy, Fergal J. ; Thompson, Ethan ; Downing, Katrina ; Suliman, Sara ; Mayanja-Kizza, Harriet ; Boom, W. Henry ; Thiel, Bonnie ; Weiner III, January ; Kaufmann, Stefan H. E. ; Dover, Drew ; Tabb, David L. ; Dockrell, Hazel M. ; Ottenhoff, Tom H. M. ; Tromp, Gerard ; Scriba, Thomas J. ; Zak, Daniel E. ; Walzl, Gerhard ; GC6-74 Consortium (2018)

CITATION: Duffy, F. J., et al. 2018. A serum circulating miRNA signature for short-term risk of progression to active tuberculosis among household contacts. Frontiers in Immunology, 9:661, doi:10.3389/fimmu.2018.00661.

The original publication is available at https://www.frontiersin.org

Article

ENGLISH ABSTRACT: Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

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