Study of CD27 and CCR4 markers on specific CD4+ T-cells as immune tools for active and latent tuberculosis management
Latorre, Irene (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Fernández Sanmartin, Marco Antonio (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Muriel-Moreno, Beatriz (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Villar-Hernández, Raquel (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Vila, Sergi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
De Souza Galvão, Maria Luiza (Hospital Universitari Vall d'Hebron)
Stojanovic, Zoran (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Jiménez-Fuentes, María A. (Hospital Universitari Vall d'Hebron)
Centeno, Carmen (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ruiz-Manzano, Juan (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Millet, Joan-Pau (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Molina-Pinargote, Israael (Serveis Clínics. Unitat Clínica de Tractament Directament Observat de la Tuberculosi)
González-Díaz, Yoel D. (Serveis Clínics. Unitat Clínica de Tractament Directament Observat de la Tuberculosi)
Lacoma, Alicia (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Luque-Chacón, Lydia (Hospital de Sant Joan Despí Moisès Broggi)
Sabriá, Josefina (Hospital de Sant Joan Despí Moisès Broggi)
Prat i Aymerich, Cristina (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Domínguez, José (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date:	2019
Abstract:	The immunological characterization of different cell markers has opened the possibility of considering them as immune tools for tuberculosis (TB) management, as they could correlate with TB latency/disease status and outcome. CD4+ T-cells producing IFN-γ+ with a low expression of CD27 have been described as an active TB marker. In addition, there are unknown homing receptors related to TB, such as CCR4, which might be useful for understanding TB pathogenesis. The aim of our study is focused on the assessment of several T-cell subsets to understand immune-mechanisms in TB. This phenotypic immune characterization is based on the study of the specific immune responses of T-cells expressing CD27 and/or CCR4 homing markers. Subjects enrolled in the study were: (i) 22 adult patients with active TB, and (ii) 26 individuals with latent TB infection (LTBI). Blood samples were drawn from each patient. The expression of CD27 and/or CCR4 markers were analyzed within CD4+ T-cells producing: (i) IFN-γ+, (ii) TNF-α+, (iii) TNF-α+IFN-γ+, and (iv) IFN-γ+ and/or TNF-α+. The percentage of CD27. within all CD4+ T-cell populations analyzed was significantly higher on active TB compared to LTBI after PPD or ESAT-6/CFP-10 stimulation. As previously reported, a ratio based on the CD27 median fluorescence intensity (MFI) was also explored (MFI of CD27 in CD4+ T-cells over MFI of CD27 in IFN-γ+CD4+ T-cells), being significantly increased during disease (p < 0. 0001 after PPD or ESAT-6/CFP-10 stimulation). This ratio was also assessed on the other CD4+ T-cells functional profiles after specific stimulation, being significantly associated with active TB. Highest diagnostic accuracies for active TB (AUC ≥ 0. 91) were achieved for: (i) CD27 within IFN-γ+TNF-α+CD4+ T-cells in response to ESAT-6/CFP-10, (ii) CD27 and CCR4 markers together within IFN-γ+CD4+ T-cells in response to PPD, and (iii) CD27 MFI ratio performed on IFN-γ+TNF-α+CD4+ T-cells after ESAT-6/CFP-10 stimulation. The lowest diagnostic accuracy was observed when CCR4 marker was evaluated alone (AUC ≤ 0. 77). CD27 and CCR4 expression detection could serve as a good method for immunodiagnosis. Moreover, the immunological characterization of markers/subset populations could be a promising tool for understanding the biological basis of the disease.
Grants:	Instituto de Salud Carlos III PI13/01546 Instituto de Salud Carlos III PI16/01912 Instituto de Salud Carlos III PI18/00411
Note:	This research was supported by: (i) a grant from the Instituto de Salud Carlos III (PI 13/01546, PI16/01912, and PI18/00411), integrated in the Plan Nacional de I+D+I and cofunded by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); and (ii) a grant from the Sociedad Española de Neumología y Cirugía Torácica (project 25/2016; SEPAR; Barcelona, Spain). JD is a researcher from the Miguel Servet programme.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió sotmesa a revisió
Published in:	Frontiers in immunology, Vol. 9 (Jan. 2019) , art. 3094, ISSN 1664-3224

DOI: 10.3389/fimmu.2018.03094
PMID: 30687314

11 p, 1.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles