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oai:repisalud.isciii.es:20.500.12105/178852024-09-21T23:31:19Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16961col_20.500.12105_16980col_20.500.12105_16985col_20.500.12105_16987

00925njm 22002777a 4500 dc Aterido, Adrià author Cañete, Juan D author Tornero, Jesús author Blanco, Francisco author Fernández-Gutierrez, Benjamín author Pérez, Carolina author Alperi-López, Mercedes author Olivè, Alex author Corominas, Héctor author Martínez-Taboada, Víctor author González, Isidoro author Fernández-Nebro, Antonio author Erra, Alba author López-Lasanta, María author López Corbeto, Mireia author Palau, Núria author Marsal, Sara author Julià, Antonio author 2019-07-02 Background: 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 10.3389/fimmu.2019.01459 1664-3224 Frontiers in immunology http://hdl.handle.net/10668/14246 31312201 http://hdl.handle.net/20.500.12105/17885 anti-TNF therapy Genomics Multi-omics association analysis Rheumatoid arthritis Transcriptomics A Combined Transcriptomic and Genomic Analysis Identifies a Gene Signature Associated With the Response to Anti-TNF Therapy in Rheumatoid Arthritis