Expression of miRNA-29a-3p and IFN-γ as biomarkers in active and latent pulmonary tuberculosis

Nirmawati Angria; Muhammad Nasrum Massi; Agussalim Bukhari; Irawaty Djaharuddin; Oslan Jumadi; Ahyar Ahmad; Upik Andriani Miskad; Rusdina Bte Ladju; Arif Santoso; Handayani Halik

doi:10.1016/j.amsu.2022.104786

Expression of miRNA-29a-3p and IFN-γ as biomarkers in active and latent pulmonary tuberculosis

Ann Med Surg (Lond). 2022 Sep 29:83:104786. doi: 10.1016/j.amsu.2022.104786. eCollection 2022 Nov.

Authors

Affiliations

¹ Doctoral Program of Biomedical Sciences, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
² Departement of Microbiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
³ Institute for Research and Community Services, Hasanuddin University, Makassar, Indonesia.
⁴ Department of Clinical Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
⁵ Department of Pulmonology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
⁶ Department of Biology, Faculty of Mathematics and Natural Sciences, State University of Makassar, Makassar, Indonesia.
⁷ Department of Chemistry, Faculty of Mathematics and Natural Sciences, Hasanuddin University, Makassar, Indonesia.
⁸ Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
⁹ Department of Biomedical Sciences, Faculty of Health Technology, Megarezky University, Makassar, Indonesia.

Abstract

Background: Diagnosis and management of latent tuberculosis (TB) infections are one of the challenges of eradicating pulmonary TB. A critical aspect of controlling pulmonary TB spread is early diagnosis. One TB biological marker type under evaluation is microRNAs (miRNAs). Mycobacterium tuberculosis infection causes epigenetic changes. The upregulation of miRNA-29a-3p suppresses the immune response by post-transcriptionally inhibiting interferon (INF)-γ expression in T cells, increasing susceptibility to pulmonary TB. This study aimed to assess miRNA-29a-3p expression as a biomarker of active and latent pulmonary TB infection.

Methods: This case-control study included 50 individuals with active TB, 33 household contacts with a positive IFN-γ release assay (IGRA), and 30 healthy controls. An enzyme-linked immunosorbent assay-based IGRA was used to determine latent pulmonary TB infection in household contacts. Quantitative real-time PCR was used to quantify miRNA-29a-3p expression. Data analysis used analyses of variance and receiver operating characteristic (ROC) curves.

Results: miRNA-29a-3p expression differed significantly between active TB, latent TB, and healthy participants (controls; p = <0.001. ROC curve analysis showed that miRNA-29a-3p expression had 86% sensitivity and 73% specificity with an area under the ROC curve (AUC) of 0.763 (95% confidence interval [CI]: 0.668-0.858). The miRNA-29a-3p ROC curve had 84.8% sensitivity and 70% specificity with an AUC of 0.808 (95% CI: 0.698-0.919) for latent TB. Additionally, miRNA-29a-3p expression was significantly correlated with active (p < 0.0001) and latent (p < 0.0001) pulmonary TB. However, miRNA-29a-3p expression was not significantly correlated with INF-γ levels in patients with active (R = 0.005; p = 0.62) and latent (R = 0.010; p = 0.38) pulmonary TB or healthy controls (R = 0.060; p = 0.19).

Conclusion: miRNA-29a-3p expression was increased in patients with active and latent pulmonary TB. Therefore, miRNA-29a-3p represents a potential biomarker for latent and active pulmonary TB. However, IFN-γ levels were not correlated with miR-29a-3p expression.

Keywords: Active pulmonary tuberculosis; IFN-γ; Latent pulmonary tuberculosis; miRNA-29a-3p.