RT Journal Article
T1 Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate
A1 Andrés, María C. de
A1 Pérez Pampín, Eva
A1 Calaza Cabanas, Manuel
A1 Santaclara, Francisco J.
A1 Ortea García, Ignacio
A1 Gómez-Reino Carnota, Juan Jesús
A1 González Martínez-Pelayo, Antonio
AB Introduction: DNA methylation is an epigenetic mechanism regulating gene expression that has been insufficientlystudied in the blood of rheumatoid arthritis (RA) patients, as only T cells and total peripheral blood mononuclearcells (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 monthafter the start of treatment with methotrexate (MTX). Analysis included DNA methylation with high-performanceliquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring(HPLC-ESI-MS/MS-SRM) and expression levels of seven methylation-specific enzymes by quantitative polymerasechain reaction (qPCR).Results: Disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients showed global DNAhypomethylation in T cells and monocytes, together with a lower expression of DNA methyltrasnferase 1 (DNMT1), themaintenance DNA methyltransferase, which was also decreased in B cells. Furthermore, significantly increasedexpression of ten-eleven translocation1 (TET1), TET2 and TET3, enzymes involved in demethylation, was found inmonocytes and of TET2 in T cells. There was also modest decreased expression of DNMT3A in B cells and of growtharrest and DNA-damage-inducible protein 45A (GADD45A) in T and B cells. Treatment with MTX revertedhypomethylation in T cells and monocytes, which were no longer different from controls, and increased globalmethylation 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 cellsubpopulations and their reversal with methotrexate treatment. These changes are accompanied by parallel changes inthe levels of enzymes involved in methylation, suggesting the possibility of regulation at this level.
PB BMC
SN 1478-6354
YR 2015
FD 2015
LK http://hdl.handle.net/10347/21479
UL http://hdl.handle.net/10347/21479
LA eng
NO de 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
NO The 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
DS Minerva
RD 28 abr 2026