A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts.


Duffy, FJ; Thompson, E; Downing, K; Suliman, S; Mayanja-Kizza, H; Boom, WH; Thiel, B; Weiner Iii, J; Kaufmann, SHE; Dover, D; Tabb, DL; Dockrell, HM; Ottenhoff, THM; Tromp, G; Scriba, TJ; Zak, DE; Walzl, G; GC6-74 Consortium, ; , COLLABORATORS; Kaufmann, SHE; Parida, SK; Golinski, R; Maertzdorf, J; Weiner, J3rd; Jacobson, M; McEwen, G; Walzl, G; Black, G; van der Spuy, G; Stanley, K; Kriel, M; Du Plessis, N; Nene, N; Loxton, A; Chegou, NN; 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, WK; Hanekom, W; Ottenhoff, THM; Klein, MR; Haks, MC; Franken, KL; Geluk, A; van Meijgaarden, KE; Joosten, SA; 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, YG; Lalor, M; Lee, JS; Crampin, AC; French, N; Ngwira, B; Smith, AB; 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; (2018) A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts. Frontiers in immunology, 9. p. 661. ISSN 1664-3224 DOI: https://doi.org/10.3389/fimmu.2018.00661

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Abstract

Biomarkers that predict who among recently <i>Mycobacterium tuberculosis</i> (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 &lt; 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.

Item Type: Article
Faculty and Department: Academic Services & Administration > Academic Administration
Research Centre: TB Centre
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PubMed ID: 29706954
URI: http://researchonline.lshtm.ac.uk/id/eprint/4647583

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