miRNA Expression Profiles in Tuberculosis – a New Study

In a study published this week in PLOS ONE, a team of scientists from China and France found that several miRNAs and their target genes may be involved in the transition from latent to active tuberculosis (TB).

Only about 5 to 10% of Mycobacterium Tuberculosis-infected individuals develop active TB at some stage in their life. The remaining approximately 90 to 95% infected people remain asymptomatic, carrying so-called latent TB infection (LTBI). Mycobacterium Tuberculosis is a causative agent of most cases of TB.  The exact underlying mechanisms of LTBI and its transition to active TB remain elusive. Currently we lack a highly sensitive and specific diagnostic for the identification of active and latent M. tuberculosis disease that can be performed at the point of care.  


Using bioinformatic tools they identified a set of 17 miRNAs whose expression is significantly different between patients with active disease and those with latent or no disease. Image credit: Wang et.al.

The researchers investigated whether miRNAs with demonstrated clinical usefulness as diagnostic or prognostic biomarkers in various malignancies and in a few nonmalignant diseases, could also be used for the diagnosis of active tuberculosis. miRNA is a type of small RNA fragments with the ability to control stability of messenger RNAs.  They used human miRNA microarrays containing more than 900 miRNAs to probe the transcriptome of peripheral blood mononuclear cells (PBMCs) in patients with active TB, latent TB infection (LTBI), and healthy controls.

Using bioinformatic tools they identified a set of 17 miRNAs whose expression is significantly different between patients with active disease and those with latent or no disease. “We believe this finding may provide a better way to diagnose active TB in the future,” the authors said.

They used similar tools to illustrate the potential regulatory mechanisms involving these miRNAs in the transition from latent to active tuberculosis. “We used the predicted target genes and previously published genome-wide transcriptional profiles of active and latent TB patients to construct the regulatory networks of miRNAs that were differentially expressed between active TB and LTBI,” the authors said. 

miRNA genes and tuberculosis-regulatory network

Illustration of the potential regulatory mechanisms involving these miRNAs in the transition from latent to active tuberculosis. Image credit: Wang et. al. 

The researchers found that several miRNAs, with previously established functions in hematopoietic cell differentiation and their target genes may be involved in the transition from latent to active TB. “These results increase the understanding of the molecular basis of LTBI and confirm that some miRNAs may control gene expression of pathways that are important for the pathogenesis of this infectious disease,” the authors added.

“Next, we will investigate whether the expression of candidate miRNAs could be correlated with the degree of disease or treatment response of the host,” they said.  Their ultimate goal is to develop a novel rapid, miRNA–based diagnostic method for active tuberculosis with high sensitivity and specificity.
 
Reference Publication: Wang C, Yang S, Sun G, Tang X, Lu S, et al. (2011) Comparative miRNA Expression Profiles in Individuals with Latent and Active Tuberculosis. PLoS ONE 6(10): e25832. doi:10.1371/journal.pone.0025832