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Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease

BACKGROUND: We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results...

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Autores principales: Essone, Paulin N., Chegou, Novel N., Loxton, Andre G., Stanley, Kim, Kriel, Magdalena, van der Spuy, Gian, Franken, Kees L., Ottenhoff, Tom H., Walzl, Gerhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099213/
https://www.ncbi.nlm.nih.gov/pubmed/25025278
http://dx.doi.org/10.1371/journal.pone.0102584
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author Essone, Paulin N.
Chegou, Novel N.
Loxton, Andre G.
Stanley, Kim
Kriel, Magdalena
van der Spuy, Gian
Franken, Kees L.
Ottenhoff, Tom H.
Walzl, Gerhard
author_facet Essone, Paulin N.
Chegou, Novel N.
Loxton, Andre G.
Stanley, Kim
Kriel, Magdalena
van der Spuy, Gian
Franken, Kees L.
Ottenhoff, Tom H.
Walzl, Gerhard
author_sort Essone, Paulin N.
collection PubMed
description BACKGROUND: We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results with short-term antigen stimulated and unstimulated culture supernatants. METHODS: We recruited 15 culture confirmed TB cases and 15 non-TB cases from a high-TB endemic community in Cape Town, South Africa into a pilot case-control study from an on-going larger study. Blood samples collected from study participants were stimulated with 4 M.tb antigens that were previously identified as promising (ESAT6/CFP10 (early secreted), Rv2029c (latency), Rv2032 (latency) and Rv2389c (rpf)) in a 7-day or overnight culture assay. Supernatants were also collected form the standard QuantiFERON In Tube (QFT-IT) test. The levels of 26 host markers were evaluated in the three culture supernatants using the Luminex platform. RESULTS: The unstimulated levels of CRP, Serum amyloid P (SAP) and serum amyloid A (SAA) and ESAT-6/CFP-10 specific IP-10 and SAA were amongst the best discriminatory markers in all 3 assays, ascertaining TB with AUC of 72–84%. Four-marker models accurately classified up to 92%, 100% and 100% of study participants in the overnight, 7-day and Quantiferon culture supernatants, respectively, after leave-one-out cross validation. CONCLUSION: Unstimulated and antigen-specific levels of CRP, SAA, IP-10, MMP-2 and sCD40L hold promise as diagnostic candidates for TB disease in short-term stimulation assays. Larger studies are required to validate these findings but the data suggest that antigen-specific cytokine production and in particular mutimarker biosignatures might contribute to future diagnostic strategies.
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spelling pubmed-40992132014-07-18 Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease Essone, Paulin N. Chegou, Novel N. Loxton, Andre G. Stanley, Kim Kriel, Magdalena van der Spuy, Gian Franken, Kees L. Ottenhoff, Tom H. Walzl, Gerhard PLoS One Research Article BACKGROUND: We previously identified Mycobacterium tuberculosis (M.tb) antigen-induced host markers that showed promise as TB diagnostic candidates in 7-day whole blood culture supernatants. The aim of the present study was to evaluate the utility of these markers further, and cross-compare results with short-term antigen stimulated and unstimulated culture supernatants. METHODS: We recruited 15 culture confirmed TB cases and 15 non-TB cases from a high-TB endemic community in Cape Town, South Africa into a pilot case-control study from an on-going larger study. Blood samples collected from study participants were stimulated with 4 M.tb antigens that were previously identified as promising (ESAT6/CFP10 (early secreted), Rv2029c (latency), Rv2032 (latency) and Rv2389c (rpf)) in a 7-day or overnight culture assay. Supernatants were also collected form the standard QuantiFERON In Tube (QFT-IT) test. The levels of 26 host markers were evaluated in the three culture supernatants using the Luminex platform. RESULTS: The unstimulated levels of CRP, Serum amyloid P (SAP) and serum amyloid A (SAA) and ESAT-6/CFP-10 specific IP-10 and SAA were amongst the best discriminatory markers in all 3 assays, ascertaining TB with AUC of 72–84%. Four-marker models accurately classified up to 92%, 100% and 100% of study participants in the overnight, 7-day and Quantiferon culture supernatants, respectively, after leave-one-out cross validation. CONCLUSION: Unstimulated and antigen-specific levels of CRP, SAA, IP-10, MMP-2 and sCD40L hold promise as diagnostic candidates for TB disease in short-term stimulation assays. Larger studies are required to validate these findings but the data suggest that antigen-specific cytokine production and in particular mutimarker biosignatures might contribute to future diagnostic strategies. Public Library of Science 2014-07-15 /pmc/articles/PMC4099213/ /pubmed/25025278 http://dx.doi.org/10.1371/journal.pone.0102584 Text en © 2014 Essone et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Essone, Paulin N.
Chegou, Novel N.
Loxton, Andre G.
Stanley, Kim
Kriel, Magdalena
van der Spuy, Gian
Franken, Kees L.
Ottenhoff, Tom H.
Walzl, Gerhard
Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease
title Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease
title_full Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease
title_fullStr Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease
title_full_unstemmed Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease
title_short Host Cytokine Responses Induced after Overnight Stimulation with Novel M. tuberculosis Infection Phase-Dependent Antigens Show Promise as Diagnostic Candidates for TB Disease
title_sort host cytokine responses induced after overnight stimulation with novel m. tuberculosis infection phase-dependent antigens show promise as diagnostic candidates for tb disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099213/
https://www.ncbi.nlm.nih.gov/pubmed/25025278
http://dx.doi.org/10.1371/journal.pone.0102584
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