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

被引：35

作者：

Duffy, Fergal J. ^{[1
]}

Thompson, Ethan ^{[1
]}

Downing, Katrina ^{[2
]}

Suliman, Sara ^{[2
]}

Mayanja-Kizza, Harriet ^{[3
,4
]}

Boom, W. Henry ^{[5
]}

Thiel, Bonnie ^{[5
]}

Weiner, January ^{[6
]}

Kaufmann, Stefan H. E. ^{[6
]}

Dover, Drew ^{[1
]}

Tabb, David L. ^{[7
,8
]}

Dockrell, Hazel M. ^{[9
]}

Ottenhoff, Tom H. M. ^{[10
]}

Tromp, Gerard ^{[7
,8
]}

Scriba, Thomas J. ^{[2
]}

Zak, Daniel E. ^{[1
]}

Walzl, Gerhard ^{[7
,8
]}

机构：

[1] Ctr Infect Dis Res, Seattle, WA 98109 USA

[2] Univ Cape Town, Inst Infect Dis & Mol Med, Dept Pathol, Div Immunol,South African TB Vaccine Initiat, Cape Town, South Africa

[3] Makerere Univ, Dept Med, Kampala, Uganda

[4] Makerere Univ, Dept Microbiol, Kampala, Uganda

[5] Case Western Reserve Univ, Cleveland, OH 44106 USA

[6] Max Planck Inst Infect Biol, Berlin, Germany

[7] Stellenbosch Univ, Fac Med & Hlth Sci, DST NRF Ctr Excellence Biomed TB Res, Tygerberg, South Africa

[8] Stellenbosch Univ, Fac Med & Hlth Sci, MRC Ctr TB Res, Div Mol Biol & Human Genet, Tygerberg, South Africa

[9] London Sch Hyg & Trop Med, Dept Immunol & Infect, London, England

[10] Leiden Univ, Med Ctr, Dept Infect Dis, Leiden, Netherlands

来源：

FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷

基金：

英国医学研究理事会; 比尔及梅琳达.盖茨基金会; 美国国家卫生研究院;

关键词：

tuberculosis; microRNA; household contact; biomarker; correlate of risk; machine learning; MICRORNAS;

D O I：

10.3389/fimmu.2018.00661

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：8

共 27 条

[1] Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma [J].