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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorJulia Cano, Antonio
dc.contributor.authorGomez Moruno, Antonio
dc.contributor.authorLopez Lasanta, Maria America
dc.contributor.authorBlanco, Francisco
dc.contributor.authorErra Duran, Alba
dc.contributor.authorFernandez-Nebro, Antonio
dc.contributor.authorMoreno Ruzafa, Estefania
dc.contributor.authorLi, Tianlu
dc.contributor.authorMartinez Mateu, Sergio Hilario
dc.contributor.authorMarsal Barril, Sara
dc.date.accessioned2022-09-09T08:18:33Z
dc.date.available2022-09-09T08:18:33Z
dc.date.issued2022-06
dc.identifier.citationJulià 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 Jun;80:104053.
dc.identifier.issn2352-3964
dc.identifier.urihttp://hdl.handle.net/11351/8094
dc.descriptionEpigenetics; Rheumatoid arthritis; Treatment response
dc.description.abstractBackground 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.
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofserieseBioMedicine;80
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectArtritis reumatoide - Tractament
dc.subjectFactor de necrosi tumoral - Inhibidors
dc.subjectADN - Metilació
dc.subject.meshArthritis, Rheumatoid
dc.subject.mesh/drug therapy
dc.subject.meshDNA Methylation
dc.subject.meshAntirheumatic Agents
dc.titleLongitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.ebiom.2022.104053
dc.subject.decsartritis reumatoide
dc.subject.decs/farmacoterapia
dc.subject.decsmetilación del ADN
dc.subject.decsantirreumáticos
dc.relation.publishversionhttps://doi.org/10.1016/j.ebiom.2022.104053
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Julià A, Gómez A, López-Lasanta M, Li T, Martínez-Mateu SH, Marsal S] Grup de Recerca en Reumatologia, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Blanco F] Rheumatology Department, INIBIC-Hospital Universitario A Coruña, A Coruña, Spain. [Erra A] Grup de Recerca en Reumatologia, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Rheumatology Department, Hospital de San Rafael, Barcelona, Spain. [Fernández-Nebro A] Rheumatology Department, Hospital Regional Universitario de Málaga, Málaga, Spain. [Moreno E] Grup de Recerca en Reumatologia, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Rheumatology Unit, Consorci Sanitari de l'Alt Penedès, Spain
dc.identifier.pmid35576644
dc.identifier.wos000805310000009
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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