Developing new TB biomarkers, are miRNA the answer?

Efforts to reduce the global TB burden are hindered by the lack of simple, reliable non-sputum based diagnostics. To date studies investigating the biomarker potential of circulating host proteins and mRNA have not shown sufficient diagnostic utility. Recently, there has been increasing interest in circulating miRNA as a biomarker of TB disease. This review examined all published miRNA-TB biomarker studies to determine if a reproducible miRNA signature of TB disease could be elucidated. From 15 miRNA profiling studies, 894 miRNA differentially expressed between TB patients and healthy controls were identified in at least one study. Of these, 143 miRNA were validated by qPCR with 53 differentially expressed between TB patients and controls. Interestingly, only 8 of these miRNA were identified in 2 or more studies, and no consensus on a reproducible miRNA signature for identification of TB disease could be identified. TB disease is clearly associated with a wide breadth of differentially expressed miRNA. This review highlights our recent progress and the multiple factors, including environment, source of tissue, ethnicity and extent of TB disease that may influence miRNA expression. Coordinated efforts are required to validate identified targets in multiple populations to progress miRNA biomarker development.