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

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. © 2018 Duffy, Thompson, Downing, Suliman, Mayanja-Kizza, Boom, Thiel, Weiner, Kaufmann, Dover, Tabb, Dockrell, Ottenhoff, Tromp, Scriba, Zak, Walzl and the GC6-74 Consortium.