dc.contributor
Institut Català de la Salut
dc.contributor
[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.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Julia Cano, Antonio
dc.contributor.author
Gomez Moruno, Antonio
dc.contributor.author
Lopez Lasanta, Maria America
dc.contributor.author
Blanco, Francisco
dc.contributor.author
Fernandez-Nebro, Antonio
dc.contributor.author
Li, Tianlu
dc.contributor.author
Martinez Mateu, Sergio Hilario
dc.contributor.author
Marsal Barril, Sara
dc.contributor.author
Moreno Ruzafa, Estefania
dc.contributor.author
Erra Duran, Alba
dc.date.accessioned
2025-10-24T08:52:57Z
dc.date.available
2025-10-24T08:52:57Z
dc.date.issued
2022-09-09T08:18:33Z
dc.date.issued
2022-09-09T08:18:33Z
dc.identifier
Julià 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
https://hdl.handle.net/11351/8094
dc.identifier
10.1016/j.ebiom.2022.104053
dc.identifier
000805310000009
dc.identifier.uri
http://hdl.handle.net/11351/8094
dc.description.abstract
Epigenetics; Rheumatoid arthritis; Treatment response
dc.description.abstract
Epigenètica; Artritis reumatoide; Resposta al tractament
dc.description.abstract
Epigenética; Artritis reumatoide; Respuesta al tratamiento
dc.description.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.
dc.description.abstract
This study was funded by the Instituto de Salud Carlos III.
dc.format
application/pdf
dc.relation
eBioMedicine;80
dc.relation
https://doi.org/10.1016/j.ebiom.2022.104053
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Artritis reumatoide - Tractament
dc.subject
Factor de necrosi tumoral - Inhibidors
dc.subject
ADN - Metilació
dc.subject
DISEASES::Musculoskeletal Diseases::Joint Diseases::Arthritis::Arthritis, Rheumatoid
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
PHENOMENA AND PROCESSES::Chemical Phenomena::Biochemical Phenomena::Alkylation::Methylation::DNA Methylation
dc.subject
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic Agents
dc.subject
ENFERMEDADES::enfermedades musculoesqueléticas::artropatías::artritis::artritis reumatoide
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
FENÓMENOS Y PROCESOS::fenómenos químicos::fenómenos bioquímicos::alquilación::metilación::metilación del ADN
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antirreumáticos
dc.title
Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
