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dc.contributor.authorAndrés, María C. de
dc.contributor.authorPérez Pampín, Eva
dc.contributor.authorCalaza Cabanas, Manuel
dc.contributor.authorSantaclara, Francisco J.
dc.contributor.authorOrtea García, Ignacio
dc.contributor.authorGómez-Reino Carnota, Juan Jesús
dc.contributor.authorGonzález Martínez-Pelayo, Antonio
dc.date.accessioned2020-04-16T18:27:44Z
dc.date.available2020-04-16T18:27:44Z
dc.date.issued2015
dc.identifier.citationde Andres, M.C., Perez-Pampin, E., Calaza, M. et al. Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate. Arthritis Res Ther 17, 233 (2015). https://doi.org/10.1186/s13075-015-0748-5
dc.identifier.issn1478-6354
dc.identifier.urihttp://hdl.handle.net/10347/21479
dc.description.abstractIntroduction: DNA methylation is an epigenetic mechanism regulating gene expression that has been insufficiently studied in the blood of rheumatoid arthritis (RA) patients, as only T cells and total peripheral blood mononuclear cells (PBMCs) from patients with established RA have been studied and with conflicting results. Method: Five major blood cell subpopulations: T, B and NK cells, monocytes, and polymorphonuclear leukocytes, were isolated from 19 early RA patients and 17 healthy controls. Patient samples were taken before and 1 month after the start of treatment with methotrexate (MTX). Analysis included DNA methylation with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring (HPLC-ESI-MS/MS-SRM) and expression levels of seven methylation-specific enzymes by quantitative polymerase chain reaction (qPCR). Results: Disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients showed global DNA hypomethylation in T cells and monocytes, together with a lower expression of DNA methyltrasnferase 1 (DNMT1), the maintenance DNA methyltransferase, which was also decreased in B cells. Furthermore, significantly increased expression of ten-eleven translocation1 (TET1), TET2 and TET3, enzymes involved in demethylation, was found in monocytes and of TET2 in T cells. There was also modest decreased expression of DNMT3A in B cells and of growth arrest and DNA-damage-inducible protein 45A (GADD45A) in T and B cells. Treatment with MTX reverted hypomethylation in T cells and monocytes, which were no longer different from controls, and increased global methylation in B cells. In addition, DNMT1 and DNMT3A showed a trend to reversion of their decreased expression. Conclusions: Our results confirm global DNA hypomethylation in patients with RA with specificity for some blood cell subpopulations and their reversal with methotrexate treatment. These changes are accompanied by parallel changes in the levels of enzymes involved in methylation, suggesting the possibility of regulation at this level.
dc.description.sponsorshipThe present work was supported by Fondo de Investigacion Sanitaria of the Instituto de Salud Carlos III (Spain), grants PI11/01048, PI12/01909 and RD12/0009/0008 that are partially financed by the European Regional Development Fund of the European Union
dc.language.isoeng
dc.publisherBMC
dc.rights© 2015 de Andres et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleAssessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate
dc.typeinfo:eu-repo/semantics/article
dc.identifier.DOI10.1186/s13075-015-0748-5
dc.relation.publisherversionhttps://doi.org/10.1186/s13075-015-0748-5
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.e-issn1478-6362
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
dc.description.peerreviewedSI


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© 2015 de Andres et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
Except where otherwise noted, this item's license is described as  © 2015 de Andres et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated





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