Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.

<h4>Background</h4>An IFN-γ response to M. tuberculosis-specific antigens is an effective biomarker for M. tuberculosis infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to M. tuberculosis antigens m...

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Main Authors: Yun-Gyoung Hur, Patricia Gorak-Stolinska, Anne Ben-Smith, Maeve K Lalor, Steven Chaguluka, Russell Dacombe, T Mark Doherty, Tom H Ottenhoff, Hazel M Dockrell, Amelia C Crampin
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0079742
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author Yun-Gyoung Hur
Patricia Gorak-Stolinska
Anne Ben-Smith
Maeve K Lalor
Steven Chaguluka
Russell Dacombe
T Mark Doherty
Tom H Ottenhoff
Hazel M Dockrell
Amelia C Crampin
author_facet Yun-Gyoung Hur
Patricia Gorak-Stolinska
Anne Ben-Smith
Maeve K Lalor
Steven Chaguluka
Russell Dacombe
T Mark Doherty
Tom H Ottenhoff
Hazel M Dockrell
Amelia C Crampin
author_sort Yun-Gyoung Hur
collection DOAJ
description <h4>Background</h4>An IFN-γ response to M. tuberculosis-specific antigens is an effective biomarker for M. tuberculosis infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to M. tuberculosis antigens may enable differentiation of latent TB from active disease.<h4>Methods</h4>Asymptomatic recently-exposed individuals (spouses of TB patients) were recruited and tuberculin skin tested, bled and followed-up for two years. Culture supernatants, from a six-day culture of diluted whole blood samples stimulated with M. tuberculosis-derived PPD or ESAT-6, were measured for IFN-γ, IL-10, IL-13, IL-17, TNF-α and CXCL10 using cytokine ELISAs. In addition, 15 patients with sputum smear-positive pulmonary TB were recruited and tested.<h4>Results</h4>Spouses with positive IFN-γ responses to M. tuberculosis ESAT-6 (>62.5 pg/mL) and TB patients showed high production of IL-17, CXCL10 and TNF-α. Higher production of IL-10 and IL-17 in response to ESAT-6 was observed in the spouses compared with TB patients while the ratios of IFN-γ/IL-10 and IFN-γ/IL-17 in response to M. tuberculosis-derived PPD were significantly higher in TB patients compared with the spouses. Tuberculin skin test results did not correlate with cytokine responses.<h4>Conclusions</h4>CXCL10 and TNF-α may be used as adjunct markers alongside an IFN-γ release assay to diagnose M. tuberculosis infection, and IL-17 and IL-10 production may differentiate individuals with LTBI from active TB.
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spelling doaj-art-e53d802a4ee04177ae61b6f92bdd97792025-08-20T03:10:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e7974210.1371/journal.pone.0079742Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.Yun-Gyoung HurPatricia Gorak-StolinskaAnne Ben-SmithMaeve K LalorSteven ChagulukaRussell DacombeT Mark DohertyTom H OttenhoffHazel M DockrellAmelia C Crampin<h4>Background</h4>An IFN-γ response to M. tuberculosis-specific antigens is an effective biomarker for M. tuberculosis infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to M. tuberculosis antigens may enable differentiation of latent TB from active disease.<h4>Methods</h4>Asymptomatic recently-exposed individuals (spouses of TB patients) were recruited and tuberculin skin tested, bled and followed-up for two years. Culture supernatants, from a six-day culture of diluted whole blood samples stimulated with M. tuberculosis-derived PPD or ESAT-6, were measured for IFN-γ, IL-10, IL-13, IL-17, TNF-α and CXCL10 using cytokine ELISAs. In addition, 15 patients with sputum smear-positive pulmonary TB were recruited and tested.<h4>Results</h4>Spouses with positive IFN-γ responses to M. tuberculosis ESAT-6 (>62.5 pg/mL) and TB patients showed high production of IL-17, CXCL10 and TNF-α. Higher production of IL-10 and IL-17 in response to ESAT-6 was observed in the spouses compared with TB patients while the ratios of IFN-γ/IL-10 and IFN-γ/IL-17 in response to M. tuberculosis-derived PPD were significantly higher in TB patients compared with the spouses. Tuberculin skin test results did not correlate with cytokine responses.<h4>Conclusions</h4>CXCL10 and TNF-α may be used as adjunct markers alongside an IFN-γ release assay to diagnose M. tuberculosis infection, and IL-17 and IL-10 production may differentiate individuals with LTBI from active TB.https://doi.org/10.1371/journal.pone.0079742
spellingShingle Yun-Gyoung Hur
Patricia Gorak-Stolinska
Anne Ben-Smith
Maeve K Lalor
Steven Chaguluka
Russell Dacombe
T Mark Doherty
Tom H Ottenhoff
Hazel M Dockrell
Amelia C Crampin
Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.
PLoS ONE
title Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.
title_full Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.
title_fullStr Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.
title_full_unstemmed Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.
title_short Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.
title_sort combination of cytokine responses indicative of latent tb and active tb in malawian adults
url https://doi.org/10.1371/journal.pone.0079742
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