Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study

Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Marc Tebruegge [verfasserIn] Nicole Ritz [verfasserIn] Susan Donath [verfasserIn] Binita Dutta [verfasserIn] Benjamin Forbes [verfasserIn] Vanessa Clifford [verfasserIn] Christel Zufferey [verfasserIn] Robert De Rose [verfasserIn] Roy M. Robins-Browne [verfasserIn] Willem Hanekom [verfasserIn] Stephen M. Graham [verfasserIn] Tom Connell [verfasserIn] Nigel Curtis [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	tuberculosis child immunoassay functional profile T cell diagnosis

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 10(2019)
Übergeordnetes Werk:	volume:10 ; year:2019

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2019.00431

Katalog-ID:	DOAJ035779837

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245	1	0	\|a Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study
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520			\|a Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone.
650		4	\|a tuberculosis
650		4	\|a child
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650		4	\|a T cell
650		4	\|a diagnosis
653		0	\|a Immunologic diseases. Allergy
700	0		\|a Marc Tebruegge \|e verfasserin \|4 aut
700	0		\|a Marc Tebruegge \|e verfasserin \|4 aut
700	0		\|a Marc Tebruegge \|e verfasserin \|4 aut
700	0		\|a Nicole Ritz \|e verfasserin \|4 aut
700	0		\|a Nicole Ritz \|e verfasserin \|4 aut
700	0		\|a Susan Donath \|e verfasserin \|4 aut
700	0		\|a Susan Donath \|e verfasserin \|4 aut
700	0		\|a Binita Dutta \|e verfasserin \|4 aut
700	0		\|a Benjamin Forbes \|e verfasserin \|4 aut
700	0		\|a Vanessa Clifford \|e verfasserin \|4 aut
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700	0		\|a Vanessa Clifford \|e verfasserin \|4 aut
700	0		\|a Christel Zufferey \|e verfasserin \|4 aut
700	0		\|a Robert De Rose \|e verfasserin \|4 aut
700	0		\|a Roy M. Robins-Browne \|e verfasserin \|4 aut
700	0		\|a Roy M. Robins-Browne \|e verfasserin \|4 aut
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700	0		\|a Stephen M. Graham \|e verfasserin \|4 aut
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700	0		\|a Tom Connell \|e verfasserin \|4 aut
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700	0		\|a Tom Connell \|e verfasserin \|4 aut
700	0		\|a Nigel Curtis \|e verfasserin \|4 aut
700	0		\|a Nigel Curtis \|e verfasserin \|4 aut
700	0		\|a Nigel Curtis \|e verfasserin \|4 aut
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author_variant	m t mt m t mt m t mt m t mt n r nr n r nr s d sd s d sd b d bd b f bf v c vc v c vc v c vc c z cz r d r rdr r m r b rmrb r m r b rmrb r m r b rmrb w h wh s m g smg s m g smg s m g smg t c tc t c tc t c tc n c nc n c nc n c nc
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allfields	10.3389/fimmu.2019.00431 doi (DE-627)DOAJ035779837 (DE-599)DOAJf6da7d74e9ad43e7b83f92a734bfa71f DE-627 ger DE-627 rakwb eng RC581-607 Marc Tebruegge verfasserin aut Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone. tuberculosis child immunoassay functional profile T cell diagnosis Immunologic diseases. Allergy Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Nicole Ritz verfasserin aut Nicole Ritz verfasserin aut Susan Donath verfasserin aut Susan Donath verfasserin aut Binita Dutta verfasserin aut Benjamin Forbes verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Christel Zufferey verfasserin aut Robert De Rose verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Willem Hanekom verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.00431 kostenfrei https://doaj.org/article/f6da7d74e9ad43e7b83f92a734bfa71f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.00431/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
spelling	10.3389/fimmu.2019.00431 doi (DE-627)DOAJ035779837 (DE-599)DOAJf6da7d74e9ad43e7b83f92a734bfa71f DE-627 ger DE-627 rakwb eng RC581-607 Marc Tebruegge verfasserin aut Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone. tuberculosis child immunoassay functional profile T cell diagnosis Immunologic diseases. Allergy Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Nicole Ritz verfasserin aut Nicole Ritz verfasserin aut Susan Donath verfasserin aut Susan Donath verfasserin aut Binita Dutta verfasserin aut Benjamin Forbes verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Christel Zufferey verfasserin aut Robert De Rose verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Willem Hanekom verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.00431 kostenfrei https://doaj.org/article/f6da7d74e9ad43e7b83f92a734bfa71f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.00431/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfields_unstemmed	10.3389/fimmu.2019.00431 doi (DE-627)DOAJ035779837 (DE-599)DOAJf6da7d74e9ad43e7b83f92a734bfa71f DE-627 ger DE-627 rakwb eng RC581-607 Marc Tebruegge verfasserin aut Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone. tuberculosis child immunoassay functional profile T cell diagnosis Immunologic diseases. Allergy Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Nicole Ritz verfasserin aut Nicole Ritz verfasserin aut Susan Donath verfasserin aut Susan Donath verfasserin aut Binita Dutta verfasserin aut Benjamin Forbes verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Christel Zufferey verfasserin aut Robert De Rose verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Willem Hanekom verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.00431 kostenfrei https://doaj.org/article/f6da7d74e9ad43e7b83f92a734bfa71f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.00431/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfieldsGer	10.3389/fimmu.2019.00431 doi (DE-627)DOAJ035779837 (DE-599)DOAJf6da7d74e9ad43e7b83f92a734bfa71f DE-627 ger DE-627 rakwb eng RC581-607 Marc Tebruegge verfasserin aut Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone. tuberculosis child immunoassay functional profile T cell diagnosis Immunologic diseases. Allergy Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Nicole Ritz verfasserin aut Nicole Ritz verfasserin aut Susan Donath verfasserin aut Susan Donath verfasserin aut Binita Dutta verfasserin aut Benjamin Forbes verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Christel Zufferey verfasserin aut Robert De Rose verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Willem Hanekom verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.00431 kostenfrei https://doaj.org/article/f6da7d74e9ad43e7b83f92a734bfa71f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.00431/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
allfieldsSound	10.3389/fimmu.2019.00431 doi (DE-627)DOAJ035779837 (DE-599)DOAJf6da7d74e9ad43e7b83f92a734bfa71f DE-627 ger DE-627 rakwb eng RC581-607 Marc Tebruegge verfasserin aut Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone. tuberculosis child immunoassay functional profile T cell diagnosis Immunologic diseases. Allergy Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Marc Tebruegge verfasserin aut Nicole Ritz verfasserin aut Nicole Ritz verfasserin aut Susan Donath verfasserin aut Susan Donath verfasserin aut Binita Dutta verfasserin aut Benjamin Forbes verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Vanessa Clifford verfasserin aut Christel Zufferey verfasserin aut Robert De Rose verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Roy M. Robins-Browne verfasserin aut Willem Hanekom verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Stephen M. Graham verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Tom Connell verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut Nigel Curtis verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 10(2019) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:10 year:2019 https://doi.org/10.3389/fimmu.2019.00431 kostenfrei https://doaj.org/article/f6da7d74e9ad43e7b83f92a734bfa71f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2019.00431/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2019
language	English
source	In Frontiers in Immunology 10(2019) volume:10 year:2019
sourceStr	In Frontiers in Immunology 10(2019) volume:10 year:2019
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	tuberculosis child immunoassay functional profile T cell diagnosis Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Marc Tebruegge @@aut@@ Nicole Ritz @@aut@@ Susan Donath @@aut@@ Binita Dutta @@aut@@ Benjamin Forbes @@aut@@ Vanessa Clifford @@aut@@ Christel Zufferey @@aut@@ Robert De Rose @@aut@@ Roy M. Robins-Browne @@aut@@ Willem Hanekom @@aut@@ Stephen M. Graham @@aut@@ Tom Connell @@aut@@ Nigel Curtis @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ035779837
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ035779837</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230501172539.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230227s2019 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3389/fimmu.2019.00431</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ035779837</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJf6da7d74e9ad43e7b83f92a734bfa71f</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC581-607</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Marc Tebruegge</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. 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callnumber-first	R - Medicine
author	Marc Tebruegge
spellingShingle	Marc Tebruegge misc RC581-607 misc tuberculosis misc child misc immunoassay misc functional profile misc T cell misc diagnosis misc Immunologic diseases. Allergy Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study
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topic_title	RC581-607 Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study tuberculosis child immunoassay functional profile T cell diagnosis
topic	misc RC581-607 misc tuberculosis misc child misc immunoassay misc functional profile misc T cell misc diagnosis misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc tuberculosis misc child misc immunoassay misc functional profile misc T cell misc diagnosis misc Immunologic diseases. Allergy
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title	Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study
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title_full	Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study
author_sort	Marc Tebruegge
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author_browse	Marc Tebruegge Nicole Ritz Susan Donath Binita Dutta Benjamin Forbes Vanessa Clifford Christel Zufferey Robert De Rose Roy M. Robins-Browne Willem Hanekom Stephen M. Graham Tom Connell Nigel Curtis
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title_sort	mycobacteria-specific mono- and polyfunctional cd4+ t cell profiles in children with latent and active tuberculosis: a prospective proof-of-concept study
callnumber	RC581-607
title_auth	Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study
abstract	Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone.
abstractGer	Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone.
abstract_unstemmed	Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone.
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title_short	Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study
url	https://doi.org/10.3389/fimmu.2019.00431 https://doaj.org/article/f6da7d74e9ad43e7b83f92a734bfa71f https://www.frontiersin.org/article/10.3389/fimmu.2019.00431/full https://doaj.org/toc/1664-3224
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author2	Marc Tebruegge Nicole Ritz Susan Donath Binita Dutta Benjamin Forbes Vanessa Clifford Christel Zufferey Robert De Rose Roy M. Robins-Browne Willem Hanekom Stephen M. Graham Tom Connell Nigel Curtis
author2Str	Marc Tebruegge Nicole Ritz Susan Donath Binita Dutta Benjamin Forbes Vanessa Clifford Christel Zufferey Robert De Rose Roy M. Robins-Browne Willem Hanekom Stephen M. Graham Tom Connell Nigel Curtis
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up_date	2024-07-03T16:56:22.228Z
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Few biomarkers with the potential to discriminate between these two infection states have been identified.Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB.Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis.Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups.Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. 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Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study

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