Identification of a plasma microRNA profile in untreated pulmonary tuberculosis patients that is modulated by anti-mycobacterial therapy

Simone E Barry; Magda Ellis; YuRong Yang; Guangyu Guan; Xiaolin Wang; Warwick J Britton; Bernadette M Saunders

doi:10.1016/j.jinf.2018.03.006

Identification of a plasma microRNA profile in untreated pulmonary tuberculosis patients that is modulated by anti-mycobacterial therapy

J Infect. 2018 Oct;77(4):341-348. doi: 10.1016/j.jinf.2018.03.006. Epub 2018 May 7.

Authors

Simone E Barry¹, Magda Ellis¹, YuRong Yang², Guangyu Guan³, Xiaolin Wang⁴, Warwick J Britton⁵, Bernadette M Saunders⁶

Affiliations

¹ Centenary Institute, The University of Sydney, Locked Bag No 6, Newtown, NSW 2042, Australia.
² Ningxia Medical University, Yinchuan, Ningxia, PR China; QIMR Berghofer Medical Research Institute, QLD, Australia.
³ Ningxia Centre for Disease Control and Prevention, Yinchuan, Ningxia, PR China.
⁴ Infectious Disease Hospital of Ningxia, Yinchuan, 7500004, PR China.
⁵ Centenary Institute, The University of Sydney, Locked Bag No 6, Newtown, NSW 2042, Australia; Discipline of Medicine, Sydney Medical School, The University of Sydney, Sydney, NSW 2006 Australia.
⁶ Centenary Institute, The University of Sydney, Locked Bag No 6, Newtown, NSW 2042, Australia; School of Life Science, University of Technology, PO Box 123, Broadway, NSW 2007, Australia. Electronic address: Bernadette.Saunders@UTS.edu.au.

PMID: 29746939
DOI: 10.1016/j.jinf.2018.03.006

Abstract

Objective: microRNA expression profiles are of interest as a biomarker of tuberculosis (TB). How anti-TB therapy effects miRNA profiles is unknown and was examined.

Methods: We identified 87 plasma miRNAs that were significantly modified in an exploratory group of 19 Chinese pulmonary TB (PTB) patients compared to 14 healthy controls. We selected 10 of these miRNAs for analysis in a cohort of 100 PTB patients prior to, and at one, two and six months during treatment.

Results: Five miRNAs were differentially expressed in PTB patients compared to controls at diagnosis; miRs -29a and -99b were up-regulated, whilst miRs -21, -146a and -652 were down-regulated. A combination of 5 miRNA distinguished TB from healthy controls with a sensitivity of 94%, a specificity of 88%, and an AUC of 0.976. Within one month of treatment, significant changes in miRs -29a, -99b, -26a and 146a levels occurred in successfully treated patients, although not all miRNAs returned to baseline by treatment completion.

Conclusion: A 5-miRNA signature shows potential for development as a novel biomarker for TB disease with potential to predict response to treatment. The failure of all miRNA to return to baseline levels may reflect ongoing remodelling in the lung parenchyma that continues after completion of anti-TB therapy.

Keywords: Anti-mycobacterial therapy; Biomarker; Disease progression; Plasma miRNA; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Antitubercular Agents / therapeutic use*
Biomarkers / blood
Case-Control Studies
Cohort Studies
Disease Progression
Female
Humans
Male
MicroRNAs / blood*
Middle Aged
Transcriptome
Treatment Outcome
Tuberculosis, Pulmonary / diagnosis*
Tuberculosis, Pulmonary / drug therapy
Up-Regulation
Young Adult

Substances

Antitubercular Agents
Biomarkers
MicroRNAs