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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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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. |
format | Online Article Text |
id | pubmed-4099213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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