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 HE;
Dover, Drew;
+8 more...Tabb, David L;
Dockrell, Hazel M;
Ottenhoff, Tom HM;
Tromp, Gerard;
Scriba, Thomas J;
Zak, Daniel E;
Walzl, Gerhard;
GC6-74 Consortium;
(2018)
A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts.
Frontiers in immunology, 9 (APR).
661-.
ISSN 1664-3224
DOI: https://doi.org/10.3389/fimmu.2018.00661
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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.