Increased frequency of circulating CD19 +CD24hiCD38hi B cells with regulatory capacity in patients with Ankylosing spondylitis (AS) naïve for biological agents
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)Publisher
Public Library of ScienceDate
2017-07-06Citation
10.1371/journal. pone.0180726
PLoS ONE 12.7 (2017): e0180726
ISSN
1932-6203DOI
10.1371/journal. pone.0180726Funded by
This work was supported by Ministerio de Economía y Competitividad/Instituto de Salud Carlos III (MINECO/ISCIII) grant numbers FIS PI-16/01189, RD12/0009/0012 and RD16/0012/0012 (RIER, RETICS Program) (http://www.idi.mineco.gob.es/portal/site/MICINN, http://www.isciii.es), by Consejería de Educación de la Comunidad de Madrid/Fondo Europeo de Desarrollo Regional RAPHYME, grant number S2010/BMD-2350 (www.madrimasd.org) and by an unrestricted research grant from Roche Pharmaceuticals (www.roche.com)Project
Gobierno de España. FIS PI-16/01189; Gobierno de España. RD12/0009/0012; Gobierno de España. RD16/0012/0012; Comunidad de Madrid. S2010/BMD-2350/RAPHYMEEditor's Version
https://doi.org/10.1371/journal. pone.0180726Subjects
Frequency of circulating; Peripheral blood; Breg cells; Anti-TNFα drugs; CD19+CD24hiCD38hi B cells; Disease activity; MedicinaRights
© 2017 Bautista-Caro et al.Abstract
Our objective was to study the frequency of circulating CD19+CD24hiCD38hi 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+CD24hiCD38hi 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+CD24hiCD38hi 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.
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Google Scholar:Bautista-Caro, María Belén
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De Miguel, Eugenio
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Peiteado, Diana
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Plasencia, Chamaida
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Villalba, Alejandro
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Monjo-Henry, Irene
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Puig-Kröger, Amaya
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Sánchez-Mateos, Paloma
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Martín-Mola, Emilio
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Miranda-Carús, María Eugenia
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