2026-05-20T04:01:54Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/232032024-11-29T01:02:39Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967col_20.500.12105_16990

00925njm 22002777a 4500 dc Rodriguez, Ramon M author Hernandez-Fuentes, Maria P author Corte-Iglesias, Viviana author Saiz, Maria Laura author Lozano, Juan Jose author Cortazar, Ana R author Mendizabal, Isabel author Suarez-Fernandez, Maria Luisa author Coto, Eliecer author Lopez-Vazquez, Antonio author Diaz-Corte, Carmen author Aransay, Ana M author Lopez-Larrea, Carlos author Suarez-Alvarez, Beatriz author 2021-08-20 Operational tolerance after kidney transplantation is defined as stable graft acceptance without the need for immunosuppression therapy. However, it is not clear which cellular and molecular pathways are driving tolerance in these patients. We performed genome-wide analysis of DNA methylation in peripheral blood mononuclear cells from kidney transplant recipients with chronic rejection and operational tolerance from the Genetic Analysis of Molecular Biomarkers of Immunological Tolerance (GAMBIT) study. Our results showed that both clinical stages diverge in 2737 genes, indicating that each one has a specific methylation signature associated with transplant outcome. We also observed that tolerance is associated with demethylation in genes involved in immune function, including B and T cell activation and Th17 differentiation, while in chronic rejection it is associated with intracellular signaling and ubiquitination pathways. Using co-expression network analysis, we selected 12 genomic regions that are specifically hypomethylated or hypermethylated in tolerant patients. Analysis of these genes in transplanted patients with low dose of steroids showed that these have a similar methylation signature to that of tolerant recipients. Overall, these results demonstrate that methylation analysis can mirror the immune status associated with transplant outcome and provides a starting point for understanding the epigenetic mechanisms associated with tolerance. Rodriguez RM, Hernandez-Fuentes MP, Corte-Iglesias V, Saiz ML, Lozano JJ, Cortazar AR, et al. Defining a Methylation Signature Associated With Operational Tolerance in Kidney Transplant Recipients. Front Immunol. 2021 Aug 20;12:709164. 10.3389/fimmu.2021.709164 1664-3224 Frontiers in Immunology https://hdl.handle.net/20.500.13003/19524 34489960 L635887351 2-s2.0-85114296918 https://hdl.handle.net/20.500.12105/23203 696578700001 Epigenetics DNA methylation Operational tolerance Kidney transplant Rejection Defining a Methylation Signature Associated With Operational Tolerance in Kidney Transplant Recipients