Mostrar o rexistro simple do ítem

dc.contributor.authorJuliá, Antonio
dc.contributor.authorGómez, Antonio
dc.contributor.authorLópez-Lasanta, María
dc.contributor.authorBlanco García, Francisco J
dc.contributor.authorErra, Alba
dc.contributor.authorFernández-Nebro, Antonio
dc.contributor.authorJuan Mas, Antonio
dc.contributor.authorPérez-García, Carolina
dc.contributor.authorGarcía Vivar, María Luz
dc.contributor.authorSánchez-Fernández, Simón
dc.contributor.authorAlperi-López, Mercedes
dc.contributor.authorSanmartí, Raimon
dc.contributor.authorOrtiz, Ana María
dc.contributor.authorMarras Fernández-Cid, Carlos
dc.contributor.authorDíaz-Torné, César
dc.contributor.authorMoreno, Estefanía
dc.contributor.authorLi, Tianlu
dc.contributor.authorMartínez-Mateu, Sergio H.
dc.contributor.authorAbsher, Devin M.
dc.contributor.authorMyers, Richard M.
dc.contributor.authorTornero Molina, Jesús
dc.contributor.authorMarsal, Sara
dc.date.accessioned2022-05-30T07:55:41Z
dc.date.available2022-05-30T07:55:41Z
dc.date.issued2022-05-13
dc.identifier.citationJuliá A, Gómez A, López-Lasanta M, Blanco F, Erra A, Fernández-Nebro A, et al. Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis. EBioMedicine. 2022;80:104053es_ES
dc.identifier.issn2352-3964
dc.identifier.urihttp://hdl.handle.net/2183/30809
dc.description.abstract[Abstract] Background: Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. Methods: Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. Findings: Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. Interpretation: Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relation.urihttps://doi-org.accedys.udc.es/10.1016/j.ebiom.2022.104053es_ES
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC-BY-NC-ND 4.0)es_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDNA methylationes_ES
dc.subjectEpigeneticses_ES
dc.subjectRheumatoid arthritises_ES
dc.subjectTNF inhibitorses_ES
dc.subjectTreatment responsees_ES
dc.titleLongitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritises_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessinfo:eu-repo/semantics/openAccesses_ES
UDC.journalTitleeBioMedicinees_ES
UDC.volume80es_ES
UDC.startPage104053es_ES


Ficheiros no ítem

Thumbnail
Thumbnail
Thumbnail

Este ítem aparece na(s) seguinte(s) colección(s)

Mostrar o rexistro simple do ítem