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

Pedersen, JL; Barry, SE; Bokil, NJ; Ellis, M; Yang, Y; Guan, G; Wang, X; Faiz, A; Britton, WJ; Saunders, BM

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

Pedersen, JL Barry, SE Bokil, NJ Ellis, M Yang, Y Guan, G Wang, X Faiz, A

Britton, WJ Saunders, BM

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Publisher:: Wiley Open Access
Publication Type:: Journal Article
Citation:: Clinical and Translational Immunology, 2021, 10, (6), pp. 1-12
Issue Date:: 2021

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Field	Value	Language
dc.contributor.author	Pedersen, JL
dc.contributor.author	Barry, SE
dc.contributor.author	Bokil, NJ
dc.contributor.author	Ellis, M
dc.contributor.author	Yang, Y
dc.contributor.author	Guan, G
dc.contributor.author	Wang, X
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Britton, WJ
dc.contributor.author	Saunders, BM
dc.date.accessioned	2022-01-11T04:43:51Z
dc.date.available	2021-05-24
dc.date.available	2022-01-11T04:43:51Z
dc.date.issued	2021
dc.identifier.citation	Clinical and Translational Immunology, 2021, 10, (6), pp. 1-12
dc.identifier.issn	2050-0068
dc.identifier.issn	2050-0068
dc.identifier.uri	http://hdl.handle.net/10453/152906
dc.description.abstract	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.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Wiley Open Access
dc.relation.ispartof	Clinical and Translational Immunology
dc.relation.isbasedon	10.1002/cti2.1298
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology, 1115 Pharmacology and Pharmaceutical Sciences
dc.title	High sensitivity and specificity of a 5-analyte protein and microRNA biosignature for identification of active tuberculosis.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	Australia
utslib.for	1107 Immunology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-01-11T04:43:49Z
pubs.issue	6
pubs.publication-status	Published
pubs.volume	10
utslib.citation.issue	6

Abstract:

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.

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http://hdl.handle.net/10453/152906