Possible relation between expression of circulating microRNA and plasma cytokine levels in cases of pulmonary tuberculosis

Abstract

Introduction: Tuberculosis (TB) is a life-threatening infection and early diagnosis is critical for treatment and prevention of transmission. There is evidence of correlation between miRNA expression and cytokine regulation during TB infection. The aim of this study was to determine the relationship between expression levels of miRNAs in plasma and cytokine levels as a potential biomarker for genetic predisposition and/or early diagnosis of TB infection.

Methodology: The expression levels of 86 miRNAs were examined in plasma samples of 44 TB patients and 44 healthy controls by qRT-PCR using BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation, South San Francisco, CA, USA) system. The levels of plasma TNF-α, IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, and IL-12/P40 were examined with ELISA.

Results: We identified dysregulation of 18 miRNAs which included upregulation of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-100-5p, miR-106b-5p, miR-128-3p, miR-133a-3p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-205-5p, miR-210-3p, and miR-296-5p, and downregulation of miR-15b-5p, miR-16-5p, and miR-25-3p in plasma samples of patients with pulmonary TB (p < 0.05). A significant correlation between the expression levels of miR-1, miR-7-5p, miR-9-5p, miR-10a-5p, miR-10b-5p, miR-15b-5p, miR-100-5p, miR-143-3p, miR-193a-5p, miR-200b-3p, miR-210-3p and cytokine levels of TNF-α, IFN-γ, IL-1β, IL-8 and IL-10 was identified (p < 0.05).

Conclusions: We demonstrated that altered expression levels of plasma miRNAs consistent with immunological response have the potential to serve as non-invasive biomarkers for early diagnosis of pulmonary TB. Additional investigations with larger sample sizes will be required to confirm our findings and to determine if miRNAs can be possible targets for TB management strategies.

Keywords: Biomarker; Cytokine; Tuberculosis; miRNA; qRT-PCR.