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Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents
Our objective was to study the frequency of circulating CD19+CD24(hi)CD38(hi) B cells (Breg) in AS patients. To this end, peripheral blood was drawn from AS patients naïve for TNF blockers (AS/nb) (n = 42) and healthy controls (HC) (n = 42). Six patients donated blood for a second time, 6 months aft...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500370/ https://www.ncbi.nlm.nih.gov/pubmed/28683133 http://dx.doi.org/10.1371/journal.pone.0180726 |
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author | Bautista-Caro, María-Belén de Miguel, Eugenio Peiteado, Diana Plasencia-Rodríguez, Chamaida Villalba, Alejandro Monjo-Henry, Irene Puig-Kröger, Amaya Sánchez-Mateos, Paloma Martín-Mola, Emilio Miranda-Carús, María-Eugenia |
author_facet | Bautista-Caro, María-Belén de Miguel, Eugenio Peiteado, Diana Plasencia-Rodríguez, Chamaida Villalba, Alejandro Monjo-Henry, Irene Puig-Kröger, Amaya Sánchez-Mateos, Paloma Martín-Mola, Emilio Miranda-Carús, María-Eugenia |
author_sort | Bautista-Caro, María-Belén |
collection | PubMed |
description | Our objective was to study the frequency of circulating CD19+CD24(hi)CD38(hi) B cells (Breg) in AS patients. To this end, peripheral blood was drawn from AS patients naïve for TNF blockers (AS/nb) (n = 42) and healthy controls (HC) (n = 42). Six patients donated blood for a second time, 6 months after initiating treatment with anti-TNFα drugs. After isolation by Ficoll-Hypaque, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by cytometry. For functional studies, total CD19+ B cells were isolated from PBMCs of 3 HC by magnetical sorting. Breg-depleted CD19+ B cells were obtained after CD19+CD24(hi)CD38(hi) B cells were removed from total CD19+ cells by cytometry. Total CD19+ B cells or Breg-depleted CD19+ B cells were established in culture and stimulated through their BCR. Secretion of IFNγ was determined by ELISA in culture supernatants. When compared with HC, AS/nb patients demonstrated a significantly increased frequency of Breg cells, which was independent of disease activity. Anti-TNFα drugs induced a significant reduction of circulating Breg numbers, which were no longer elevated after six months of treatment. Functional in vitro studies showed that the secretion of IFNγ was significantly higher in Breg-depleted as compared with total CD19+ B cells, indicating that Breg can downmodulate B cell pro-inflammatory cytokine secretion. In summary, an increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells is observed in AS/nb patients, that is not related with disease activity; anti-TNFα drugs are able to downmodulate circulating Breg numbers in AS. |
format | Online Article Text |
id | pubmed-5500370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55003702017-07-11 Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents Bautista-Caro, María-Belén de Miguel, Eugenio Peiteado, Diana Plasencia-Rodríguez, Chamaida Villalba, Alejandro Monjo-Henry, Irene Puig-Kröger, Amaya Sánchez-Mateos, Paloma Martín-Mola, Emilio Miranda-Carús, María-Eugenia PLoS One Research Article Our objective was to study the frequency of circulating CD19+CD24(hi)CD38(hi) B cells (Breg) in AS patients. To this end, peripheral blood was drawn from AS patients naïve for TNF blockers (AS/nb) (n = 42) and healthy controls (HC) (n = 42). Six patients donated blood for a second time, 6 months after initiating treatment with anti-TNFα drugs. After isolation by Ficoll-Hypaque, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by cytometry. For functional studies, total CD19+ B cells were isolated from PBMCs of 3 HC by magnetical sorting. Breg-depleted CD19+ B cells were obtained after CD19+CD24(hi)CD38(hi) B cells were removed from total CD19+ cells by cytometry. Total CD19+ B cells or Breg-depleted CD19+ B cells were established in culture and stimulated through their BCR. Secretion of IFNγ was determined by ELISA in culture supernatants. When compared with HC, AS/nb patients demonstrated a significantly increased frequency of Breg cells, which was independent of disease activity. Anti-TNFα drugs induced a significant reduction of circulating Breg numbers, which were no longer elevated after six months of treatment. Functional in vitro studies showed that the secretion of IFNγ was significantly higher in Breg-depleted as compared with total CD19+ B cells, indicating that Breg can downmodulate B cell pro-inflammatory cytokine secretion. In summary, an increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells is observed in AS/nb patients, that is not related with disease activity; anti-TNFα drugs are able to downmodulate circulating Breg numbers in AS. Public Library of Science 2017-07-06 /pmc/articles/PMC5500370/ /pubmed/28683133 http://dx.doi.org/10.1371/journal.pone.0180726 Text en © 2017 Bautista-Caro et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bautista-Caro, María-Belén de Miguel, Eugenio Peiteado, Diana Plasencia-Rodríguez, Chamaida Villalba, Alejandro Monjo-Henry, Irene Puig-Kröger, Amaya Sánchez-Mateos, Paloma Martín-Mola, Emilio Miranda-Carús, María-Eugenia Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents |
title | Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents |
title_full | Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents |
title_fullStr | Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents |
title_full_unstemmed | Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents |
title_short | Increased frequency of circulating CD19+CD24(hi)CD38(hi) B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents |
title_sort | increased frequency of circulating cd19+cd24(hi)cd38(hi) b cells with regulatory capacity in patients with ankylosing spondylitis (as) naïve for biological agents |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500370/ https://www.ncbi.nlm.nih.gov/pubmed/28683133 http://dx.doi.org/10.1371/journal.pone.0180726 |
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