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dc.contributor.authorSester, Urban
dc.contributor.authorFousse, Mathias
dc.contributor.authorDirks, Jan
dc.contributor.authorMack, Ulrich
dc.contributor.authorPrasse, Antje
dc.contributor.authorSingh, Mahavir
dc.contributor.authorLalvani, Ajit
dc.contributor.authorSester, Martina
dc.date.accessioned2011-08-29T12:55:10Z
dc.date.available2011-08-29T12:55:10Z
dc.date.issued2011
dc.identifier.citationWhole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states. 2011, 6 (3):e17813 PLoS ONEen
dc.identifier.issn1932-6203
dc.identifier.pmid21423578
dc.identifier.doi10.1371/journal.pone.0017813
dc.identifier.urihttp://hdl.handle.net/10033/141115
dc.description.abstractT-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.
dc.language.isoenen
dc.subject.meshAntigens, Bacterialen
dc.subject.meshBacterial Proteinsen
dc.subject.meshCD4-Positive T-Lymphocytesen
dc.subject.meshDemographyen
dc.subject.meshDiagnosis, Differentialen
dc.subject.meshFemaleen
dc.subject.meshFlow Cytometryen
dc.subject.meshHumansen
dc.subject.meshInterferon-gammaen
dc.subject.meshInterleukin-2en
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshTuberculosisen
dc.titleWhole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states.en
dc.typeArticleen
dc.contributor.departmentDepartment of Internal Medicine IV, Saarland University, Homburg, Germany.en
dc.identifier.journalPloS oneen
refterms.dateFOA2018-06-12T17:53:34Z
html.description.abstractT-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.


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