High sensitivity and specificity of a 5‐analyte protein and microRNA biosignature for identification of active tuberculosis

High sensitivity and specificity of a 5‐analyte protein and microRNA biosignature for identification of active tuberculosis.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1002/cti2.1298
Journal or Publication Title: Clinical & Translational Immunology
Volume: 10
Number: 6
Date: 22 June 2021
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1002/cti2.1298
ISSN: 2050-0068
Date Deposited: 10 Oct 2021 10:08

Objectives: Non-sputum-based tests to accurately identify active tuberculosis (TB) disease and monitor response to therapy are urgently needed. This study examined the biomarker capacity of a panel of plasma proteins alone, and in conjunction with a previously identified miRNA signature, to identify active TB disease.

Methods: The expression of nine proteins (IP-10, MCP-1, sTNFR1, RANTES, VEGF, IL-6, IL-10, TNF and Eotaxin) was measured in the plasma of 100 control subjects and 100 TB patients, at diagnosis (treatment naïve) and over the course of treatment (1-, 2- and 6-month intervals). The diagnostic performance of the nine proteins alone, and with the miRNA, was assessed.

Results: Six proteins were significantly up-regulated in the plasma of TB patients at diagnosis compared to controls. Receiver operator characteristic curve analysis demonstrated that IP-10 with an AUC = 0.874, sensitivity of 75% and specificity of 87% was the best single biomarker candidate to distinguish TB patients from controls. IP-10 and IL-6 levels fell significantly within one month of commencing treatment and may have potential as indicators of a positive response to therapy. The combined protein and miRNA panel gave an AUC of 1.00. A smaller panel of only five analytes (IP-10, miR-29a, miR-146a, miR-99b and miR-221) showed an AUC = 0.995, sensitivity of 96% and specificity of 97%.

Conclusions: A novel combination of miRNA and proteins significantly improves the sensitivity and specificity as a biosignature over single biomarker candidates and may be useful for the development of a non-sputum test to aid the diagnosis of active TB disease.

Keywords: diagnosis; microRNA; plasma biomarkers; proteins; tuberculosis.

© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Pedersen, Jessica L
Barry, Simone E
Bokil, Nilesh J
Ellis, Magda
Yang, YuRong
Guan, Guangyu
Wang, Xiaolin
Faiz, Alen
Britton, Warwick J
Saunders, Bernadette M
Last Modified: 10 Oct 2021 10:08
URI: https://eprints.centenary.org.au/id/eprint/1135

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