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.author | Essone, Paulin N. | en_ZA |
dc.contributor.author | Chegou, Novel N. | en_ZA |
dc.contributor.author | Loxton, Andre G. | en_ZA |
dc.contributor.author | Stanley, Kim | en_ZA |
dc.contributor.author | Kriel, Magdalena | en_ZA |
dc.contributor.author | Van der Spuy, Gian | en_ZA |
dc.contributor.author | Franken, Kees L. | en_ZA |
dc.contributor.author | Ottenhoff, Tom H. | en_ZA |
dc.contributor.author | Walzl, Gerhard | en_ZA |
dc.date.accessioned | 2016-03-07T06:27:36Z | |
dc.date.available | 2016-03-07T06:27:36Z | |
dc.date.issued | 2014-07-15 | |
dc.description | Please 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.description | The original publication is available at http://journals.plos.org/plosone | en_ZA |
dc.description.abstract | 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. | en_ZA |
dc.description.uri | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102584 | |
dc.description.version | Publisher's version | en_ZA |
dc.format.extent | 16 pages | en_ZA |
dc.identifier.citation | 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.identifier.issn | 1932-6203 (online) | |
dc.identifier.other | doi:10.1371/journal.pone.0102584. | |
dc.identifier.uri | http://hdl.handle.net/10019.1/98255 | |
dc.language.iso | en_ZA | en_ZA |
dc.publisher | PLoS | en_ZA |
dc.rights.holder | Authors retain copyright | en_ZA |
dc.subject | Mycobacterium tuberculosis | en_ZA |
dc.subject | Mycobacterium tuberculosis -- Diagnosis | en_ZA |
dc.title | Host cytokine responses induced after overnight stimulation with novel M. tuberculosis infection phase-dependent antigens show promise as diagnostic candidates for TB disease | en_ZA |
dc.type | Article | en_ZA |