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B-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis

2017Journal article Open access
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dc.contributor.authorMoura, Rita
dc.contributor.authorQuaresma, Cláudia
dc.contributor.authorVieira, Ana R.
dc.contributor.authorGonçalves, Maria João
dc.contributor.authorPolido Pereira, Joaquim
dc.contributor.authorRomão, Vasco C.
dc.contributor.authorMartins, Nádia
dc.contributor.authorCanhao, Helena
dc.contributor.authorFonseca, João Eurico
dc.date.accessioned2022-09-08T11:53:32Z
dc.date.available2022-09-08T11:53:32Z
dc.date.issued2017
dc.descriptionCopyright: © 2017 Moura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.pt_PT
dc.description.abstractBackground: The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA. Methods: Blood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors. B-cell subpopulations were characterized by flow cytometry and B-cell gene expression was analyzed by real-time PCR on isolated B-cells. Serum levels of BAFF, CXCL13 and sCD23 were determined by ELISA. Results: The frequency of total CD19+ B cells in circulation was similar between controls and all RA groups, irrespective of treatment, but double negative (DN) IgD-CD27- memory B cells were significantly increased in ERA and established RA when compared to controls. Treatment with TNF-inhibitors and tocilizumab restored the frequency of IgD-CD27- B-cells to normal levels, but did not affect other B cell subpopulations. TACI, CD95, CD5, HLA-DR and TLR9 expression on B-cells significantly increased after treatment with either TNF-inhibitors and/ or tocilizumab, but no significant changes were observed in BAFF-R, BCMA, CD69, CD86, CXCR5, CD23, CD38 and IgM expression on B-cells when comparing baseline with post-treatment follow-ups. Alterations in B-cell gene expression of BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M were found in ERA and established RA patients, but no significant differences were observed after TNF-inhibitors and tocilizumab treatment when comparing baseline and follow-ups. Serum levels of CXCL13, sCD23 and BAFF were not significantly affected by treatment with TNF-inhibitors and tocilizumab. Conclusions: In RA patients, the use of TNF-inhibitors and/ or tocilizumab treatment affects B-cell phenotype and IgD-CD27- memory B cells in circulation, but not B-cell gene expression levels.pt_PT
dc.description.sponsorshipRAM was funded by Fundação para a Ciência e a Tecnologia (FCT, www.fct.pt) (SFRH/BPD/81936/2011), Portugal.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPLoS One. 2017 Sep 8;12(9):e0182927pt_PT
dc.identifier.doi10.1371/journal.pone.0182927pt_PT
dc.identifier.eissn1932-6203
dc.identifier.urihttp://hdl.handle.net/10451/54374
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relationTHE ROLE OF AUTOREACTIVE 9G4+ B CELLS IN RHEUMATOID ARTHRITIS ONSET AND CLINICAL RELAPSE AFTER TREATMENT
dc.relation.publisherversionhttps://journals.plos.org/plosone/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleB-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleTHE ROLE OF AUTOREACTIVE 9G4+ B CELLS IN RHEUMATOID ARTHRITIS ONSET AND CLINICAL RELAPSE AFTER TREATMENT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F81936%2F2011/PT
oaire.citation.issue9pt_PT
oaire.citation.titlePLOS ONEpt_PT
oaire.citation.volume12pt_PT
person.familyNameMoura
person.familyNameGonçalves
person.familyNamePolido Pereira
person.familyNameC Romão
person.familyNameCanhao
person.familyNameFonseca
person.givenNameRita
person.givenNameMaria João
person.givenNameJoaquim
person.givenNameVasco
person.givenNameHelena
person.givenNameJoão
person.identifier503714
person.identifier676523
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person.identifier.ciencia-idF21E-178E-DB12
person.identifier.ciencia-id9812-232A-B282
person.identifier.ciencia-id771D-0A5C-626B
person.identifier.ciencia-idF310-B85D-57C7
person.identifier.orcid0000-0002-9685-6924
person.identifier.orcid0000-0001-6461-9142
person.identifier.orcid0000-0002-7188-8516
person.identifier.orcid0000-0002-5603-9436
person.identifier.orcid0000-0002-3239-2809
person.identifier.orcid0000-0003-1432-3671
person.identifier.ridO-8224-2014
person.identifier.scopus-author-id23480391100
person.identifier.scopus-author-id55989452300
person.identifier.scopus-author-id6602393492
person.identifier.scopus-author-id7101983519
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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