Mostrar o rexistro simple do ítem

dc.contributor.authorAterido, Adria
dc.contributor.authorCanete, Juan D
dc.contributor.authorTornero, Jesus
dc.contributor.authorBLANCO GARCIA, FRANCISCO JAVIER 
dc.contributor.authorFernandez-Gutierrez, Benjamin
dc.contributor.authorPerez, Carolina
dc.contributor.authorAlperi-Lopez, Mercedes
dc.contributor.authorOlive, Alex
dc.contributor.authorCorominas, Hector
dc.contributor.authorMartinez-Taboada, Victor
dc.contributor.authorGonzalez, Isidoro
dc.contributor.authorFernandez-Nebro, Antonio
dc.contributor.authorErra, Alba
dc.contributor.authorLopez-Lasanta, Maria
dc.contributor.authorLopez Corbeto, Mireia
dc.contributor.authorPalau, Nuria
dc.contributor.authorMarsal, Sara
dc.contributor.authorJulia, Antonio
dc.date.accessioned2022-01-25T12:17:42Z
dc.date.available2022-01-25T12:17:42Z
dc.date.issued2019
dc.identifier.issn1664-3224
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614444/pdf/fimmu-10-01459.pdfes
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/31312201es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/15927
dc.description.abstractBackground: Rheumatoid arthritis (RA) is the most frequent autoimmune disease involving the joints. Although anti-TNF therapies have proven effective in the management of RA, approximately one third of patients do not show a significant clinical response. The objective of this study was to identify new genetic variation associated with the clinical response to anti-TNF therapy in RA. Methods: We performed a sequential multi-omic analysis integrating different sources of molecular information. First, we extracted the RNA from synovial biopsies of 11 RA patients starting anti-TNF therapy to identify gene coexpression modules (GCMs) in the RA synovium. Second, we analyzed the transcriptomic association between each GCM and the clinical response to anti-TNF therapy. The clinical response was determined at week 14 using the EULAR criteria. Third, we analyzed the association between the GCMs and anti-TNF response at the genetic level. For this objective, we used genome-wide data from a cohort of 348 anti-TNF treated patients from Spain. The GCMs that were significantly associated with the anti-TNF response were then tested for validation in an independent cohort of 2,706 anti-TNF treated patients. Finally, the functional implication of the validated GCMs was evaluated via pathway and cell type epigenetic enrichment analyses. Results: A total of 149 GCMs were identified in the RA synovium. From these, 13 GCMs were found to be significantly associated with anti-TNF response (P < 0.05). At the genetic level, we detected two of the 13 GCMs to be significantly associated with the response to adalimumab (P = 0.0015) and infliximab (P = 0.021) in the Spain cohort. Using the independent cohort of RA patients, we replicated the association of the GCM associated with the response to adalimumab (P = 0.0019). The validated module was found to be significantly enriched for genes involved in the nucleotide metabolism (P = 2.41e-5) and epigenetic marks from immune cells, including CD4+ regulatory T cells (P = 0.041). Conclusions: These findings show the existence of a drug-specific genetic basis for anti-TNF response, thereby supporting treatment stratification in the search for response biomarkers in RA.en
dc.language.isoenges
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshTumor Necrosis Factor-alpha*
dc.subject.meshHumans*
dc.subject.meshTreatment Outcome*
dc.subject.meshAntirheumatic Agents*
dc.subject.meshGenome-Wide Association Study*
dc.subject.meshTranscriptome*
dc.subject.meshBiopsy*
dc.subject.meshSynovial Membrane*
dc.subject.meshArthritis*
dc.subject.meshCohort Studies*
dc.subject.meshGene Regulatory Networks*
dc.titleA Combined Transcriptomic and Genomic Analysis Identifies a Gene Signature Associated With the Response to Anti-TNF Therapy in Rheumatoid Arthritisen
dc.typeArtigoes
dc.identifier.doi10.3389/fimmu.2019.01459
dc.identifier.pmid31312201
dc.identifier.sophos32391
dc.journal.titleFrontiers in Immunologyes
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de A Coruña - Complexo Hospitalario Universitario de A Coruña::Reumatoloxíaes
dc.rights.accessRightsopenAccesses
dc.subject.decsresultado del tratamiento*
dc.subject.decsmembrana sinovial*
dc.subject.decstranscriptoma*
dc.subject.decsfactor de necrosis tumoral alfa*
dc.subject.decsbiopsia*
dc.subject.decshumanos*
dc.subject.decsestudio de asociación genómica completa*
dc.subject.decsestudios de cohortes*
dc.subject.decsantirreumáticos*
dc.subject.decsredes génicas reguladoras*
dc.subject.decsartritis*
dc.subject.keywordCHUACes
dc.typefidesArtículo Originales
dc.typesophosArtículo Originales
dc.volume.number10es


Ficheiros no ítem

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

Mostrar o rexistro simple do ítem

Atribución 4.0 Internacional
A non ser que se indique outra cousa, a licenza do ítem descríbese comoAtribución 4.0 Internacional