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          Institute: MPI für Infektionsbiologie     Collection: Department of Immunology     Display Documents



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ID: 611153.0, MPI für Infektionsbiologie / Department of Immunology
Potential of Host Markers Produced by Infection Phase-Dependent Antigen-Stimulated Cells for the Diagnosis of Tuberculosis in a Highly Endemic Area
Authors:Chegou, Novel N.; Essone, Paulin N.; Loxton, Andre G.; Stanley, Kim; Black, Gillian F.; van der Spuy, Gian D.; van Helden, Paul D.; Franken, Kees L.; Parida, Shreemanta K.; Klein, Michel R.; Kaufmann, Stefan H. E.; Ottenhoff, Tom H. M.; Walzl, Gerhard
Language:English
Date of Publication (YYYY-MM-DD):2012-06-05
Title of Journal:PLoS ONE
Journal Abbrev.:PLoS One
Volume:7
Issue / Number:6
Sequence Number of Article:e38501
Copyright:Copyright Chegou et al. 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 credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Background: Recent interferon gamma (IFN-gamma)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-gamma, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-alpha were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-gamma in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays.
Comment of the Author/Creator:Funding: This work was supported by the Bill & Melinda Gates Foundation through Grand Challenge 6 (BMGFGC6, grant no 37772).
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Immunology
External Affiliations:[Chegou, Novel N.; Essone, Paulin N.; Loxton, Andre G.; Stanley, Kim; Black, Gillian F.; van der Spuy, Gian D.; van Helden, Paul D.; Walzl, Gerhard] Univ Stellenbosch, Fac Hlth Sci, DST NRF Ctr Excellence Biomed TB Res, ZA-7505 Tygerberg, South Africa.; [Chegou, Novel N.; Essone, Paulin N.; Loxton, Andre G.; Stanley, Kim; Black, Gillian F.; van der Spuy, Gian D.; van Helden, Paul D.; Walzl, Gerhard] Univ Stellenbosch, Fac Hlth Sci, MRC Ctr Mol & Cellular Biol, Div Mol Biol & Human Genet,Dept Biomed Sci, ZA-7505 Tygerberg, South Africa.; [Franken, Kees L.; Klein, Michel R.; Ottenhoff, Tom H. M.] Leiden Univ, Med Ctr, Dept Infect Dis, Leiden, Netherlands.
Identifiers:ISI:000305343900050 [ID No:1]
ISSN:1932-6203 [ID No:2]
DOI:10.1371/journal.pone.0038501 [ID No:3]
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