Expression levels of candidate circulating microRNAs in pediatric tuberculosis

ABSTRACT

Tuberculosis (TB) is a preventable and curable disease, but increased mortality and morbidity associated with TB is one of the leading causes of deaths worldwide. MicroRNAs (miRNAs) are small, non-coding RNAs known to regulate the host immune response against TB. We investigated the expression profile of candidate circulating miRNAs, which could be used as a blood biomarker for the effective diagnosis of pediatric tuberculosis. A cross-sectional comparative study was conducted, including 30 children with active-TB and 30 healthy controls (HC) in a tertiary care hospital in Puducherry. We used the SYBR green-based miScript qRT-PCR assay to analyze the expression levels of miRNAs in plasma. Further, we used the receiver operating characteristic curve (ROC) to evaluate the diagnostic value of miRNAs. Active-TB included 25 (83.3%) pulmonary TB and 5 (16.7%) extrapulmonary TB cases. We found a significant upregulation of miR-21, miR-29a, miR-31, miR-155, and downregulation of miR-146a in children with active-TB compared to HC. The ROC analysis showed an excellent diagnostic value of miRNAs as follows: miR‑31> miR‑155> miR‑146a with AUC of (95% CI) miRNAs 0.978, 0.953, and 0.903, respectively. Altered circulating miRNA expression levels could be involved in the dysregulation of the host immune response to TB. The ROC analysis indicated that miRNAs miR-31, miR-155 and miR-146a could be effective diagnostic biomarkers for the detection of active-TB in children.

KEYWORDS:

• Tuberculosis
• mycobacterium tuberculosis
• microrna
• TB diagnosis
• pediatric TB
• biomarker

Acknowledgments

The authors much acknowledge the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) – Intramural Research Grant for financial support. The authors sincerely thank all the patients, their families, and the healthy volunteers for their participation.

Author contributions

All authors are equally contributed to study conception and design. Material preparation, data collection, analysis, and experiments were performed by Mr. Kathirvel M and Mrs. Saranya S. The first draft of the manuscript was written by Mr. Kathirvel M. Manuscript review, editing, and correction were done by Dr. S. Mahadevan. All authors have read and approved the final manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Ethical conduct of research

The study was reviewed by the institute ethics committee of the tertiary care hospital (JIP/IEC/2014/10/491). All the children and their parents were signed in an informed consent form to participate in the study.