RT Journal Article
T1 Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis.
A1 Julia, Antonio
A1 Gomez, Antonio
A1 Lopez-Lasanta, Maria
A1 Blanco, Francisco
A1 Erra, Alba
A1 Fernandez-Nebro, Antonio
A1 Mas, Antonio Juan
A1 Perez-Garcia, Carolina
A1 Garcia-Vivar, Ma Luz
A1 Sanchez-Fernandez, Simon
A1 Alperi-Lopez, Mercedes
A1 Sanmarti, Raimon
A1 Ortiz, Ana Maria
A1 Fernandez-Cid, Carlos Marras
A1 Diaz-Torne, Cesar
A1 Moreno, Estefania
A1 Li, Tianlu
A1 Martinez-Mateu, Sergio H
A1 Absher, Devin M
A1 Myers, Richard M
A1 Molina, Jesus Tornero
A1 Marsal, Sara
K1 DNA methylation
K1 Epigenetics
K1 Rheumatoid arthritis
K1 TNF inhibitors
K1 Treatment response
AB 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. 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. Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR 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. The Instituto de Salud Carlos III.
PB Elsevier
YR 2022
FD 2022-05-13
LK http://hdl.handle.net/10668/22163
UL http://hdl.handle.net/10668/22163
LA en
NO 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
DS RISalud
RD Apr 18, 2025