AUTHOR=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 , the GC6-74 Consortium , Kaufmann S. H. E. , Parida S. K. , Golinski R. , Maertzdorf J. , Weiner J. , Jacobson M. , McEwen G. , Walzl G. , Black G. , van der Spuy G. , Stanley K. , Kriel M. , Du Plessis N. , Nene N. , Loxton A. , Chegou N. N. , Suliman S. , Scriba T. , Mahomed H. , Erasmus M. , Xasa O. , Veldsman A. , Hughes J. , Downing K. , Penn-Nicholson A. , Mulenga H. , Abel B. , Bowmaker M. , Kagina B. , C W. Kwong , Hanekom W. , Ottenhoff T. H. M. , Klein M. R. , Haks M. C. , Franken K. L. , Geluk A. , van Meijgaarden K. E. , Joosten S. A. , van Baarle D. , Miedema F. , H. Boom W. , Thiel B. , Sadoff J. , Sizemore D. , Ramachandran S. , Barker L. , Brennan M. , Weichold F. , Muller S. , Geiter L. , Schoolnik G. , Dolganov G. , Van T. , Mayanja-Kizza H. , Joloba M. , Zalwango S. , Nsereko M. , Okwera B. , Kisingo H. , Dockrell H. , Smith S. , Gorak-Stolinska P. , Hur Y.-G. , Lalor M. , Lee J.-S. , Crampin A. C. , French N. , Ngwira B. , Smith A. B. , Watkins K. , Ambrose L. , Simukonda F. , Mvula H. , Chilongo F. , Saul J. , Branson K. , Kassa D. , Abebe A. , Mesele T. , Tegbaru B. , Howe R. , Mihret A. , Aseffa A. , Bekele Y. , Iwnetu R. , Tafesse M. , Yamuah L. , Ota M. , Sutherland J. , Hill P. , Adegbola R. , Corrah T. , Antonio M. , Togun T. , Adetifa I. , Donkor S. , Andersen P. , Rosenkrands I. , Doherty M. , Weldingh K. TITLE=A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00661 DOI=10.3389/fimmu.2018.00661 ISSN=1664-3224 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.