Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.

<h4>Objective</h4>To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients.<h4>Methods</h4>CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from...

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Autores principales:	Irene Arroyo-Villa, María-Belén Bautista-Caro, Alejandro Balsa, Pilar Aguado-Acín, Laura Nuño, María-Gema Bonilla-Hernán, Amaya Puig-Kröger, Emilio Martín-Mola, María-Eugenia Miranda-Carús
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e22bc4a9fa634c9e9173ca1c0ecc2ea3
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spelling	oai:doaj.org-article:e22bc4a9fa634c9e9173ca1c0ecc2ea32021-11-18T07:09:50ZFrequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.1932-620310.1371/journal.pone.0042189https://doaj.org/article/e22bc4a9fa634c9e9173ca1c0ecc2ea32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22870298/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients.<h4>Methods</h4>CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-γ, TNF-α and IL-10 were measured by ELISA in cell-free supernatants.<h4>Results</h4>When all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-γ, TNF-α and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC.<h4>Conclusion</h4>Decreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate.Irene Arroyo-VillaMaría-Belén Bautista-CaroAlejandro BalsaPilar Aguado-AcínLaura NuñoMaría-Gema Bonilla-HernánAmaya Puig-KrögerEmilio Martín-MolaMaría-Eugenia Miranda-CarúsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42189 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irene Arroyo-Villa María-Belén Bautista-Caro Alejandro Balsa Pilar Aguado-Acín Laura Nuño María-Gema Bonilla-Hernán Amaya Puig-Kröger Emilio Martín-Mola María-Eugenia Miranda-Carús Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.
description	<h4>Objective</h4>To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients.<h4>Methods</h4>CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-γ, TNF-α and IL-10 were measured by ELISA in cell-free supernatants.<h4>Results</h4>When all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-γ, TNF-α and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC.<h4>Conclusion</h4>Decreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate.
format	article
author	Irene Arroyo-Villa María-Belén Bautista-Caro Alejandro Balsa Pilar Aguado-Acín Laura Nuño María-Gema Bonilla-Hernán Amaya Puig-Kröger Emilio Martín-Mola María-Eugenia Miranda-Carús
author_facet	Irene Arroyo-Villa María-Belén Bautista-Caro Alejandro Balsa Pilar Aguado-Acín Laura Nuño María-Gema Bonilla-Hernán Amaya Puig-Kröger Emilio Martín-Mola María-Eugenia Miranda-Carús
author_sort	Irene Arroyo-Villa
title	Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.
title_short	Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.
title_full	Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.
title_fullStr	Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.
title_full_unstemmed	Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.
title_sort	frequency of th17 cd4+ t cells in early rheumatoid arthritis: a marker of anti-ccp seropositivity.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e22bc4a9fa634c9e9173ca1c0ecc2ea3
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Frequency of Th17 CD4+ T cells in early rheumatoid arthritis: a marker of anti-CCP seropositivity.

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