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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

dc.contributor.authorEssone, Paulin N.en_ZA
dc.contributor.authorChegou, Novel N.en_ZA
dc.contributor.authorLoxton, Andre G.en_ZA
dc.contributor.authorStanley, Kimen_ZA
dc.contributor.authorKriel, Magdalenaen_ZA
dc.contributor.authorVan der Spuy, Gianen_ZA
dc.contributor.authorFranken, Kees L.en_ZA
dc.contributor.authorOttenhoff, Tom H.en_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.date.accessioned2016-03-07T06:27:36Z
dc.date.available2016-03-07T06:27:36Z
dc.date.issued2014-07-15
dc.identifier.citationEssone, P. N. et al. 2014. Host cytokine responses induced after overnight stimulation with novel M. tuberculosis infection phase-dependent antigens show promise as diagnostic candidates for TB disease. PLoS ONE, 9(7):e102584, doi:10.1371/journal.pone. 0102584.en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0102584.
dc.identifier.urihttp://hdl.handle.net/10019.1/98255
dc.descriptionPlease cite as follows: Essone, P. N. et al. 2014. Host cytokine responses induced after overnight stimulation with novel M. tuberculosis infection phase-dependent antigens show promise as diagnostic candidates for TB disease. PLoS ONE, 9(7):e102584, doi:10.1371/journal.pone. 0102584.en_ZA
dc.descriptionThe original publication is available at http://journals.plos.org/plosoneen_ZA
dc.description.abstractBackground: 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.en_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102584
dc.format.extent16 pagesen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherPLoSen_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectMycobacterium tuberculosis -- Diagnosisen_ZA
dc.titleHost cytokine responses induced after overnight stimulation with novel M. tuberculosis infection phase-dependent antigens show promise as diagnostic candidates for TB diseaseen_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's versionen_ZA
dc.rights.holderAuthors retain copyrighten_ZA


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