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

Front Immunol. 2018 Apr 13:9:661. doi: 10.3389/fimmu.2018.00661. eCollection 2018.


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.

Keywords: biomarker; correlate of risk; household contact; machine learning; microRNA; tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Circulating MicroRNA / blood*
  • Contact Tracing
  • Disease Progression
  • Female
  • Humans
  • Machine Learning
  • Male
  • Mycobacterium tuberculosis
  • Risk
  • South Africa / epidemiology
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / genetics*
  • Uganda / epidemiology
  • Young Adult


  • Biomarkers
  • Circulating MicroRNA