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| Pàgina inicial > Articles > Articles publicats > Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids |
(Instituto de Parasitología y Biomedicina "López-Neyra") (Instituto de Parasitología y Biomedicina "López-Neyra") (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Instituto de Parasitología y Biomedicina "López-Neyra") (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Instituto de Investigación Sanitaria de Granada) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Instituto de Parasitología y Biomedicina "López-Neyra")
| Data: | 2022 |
| Resum: | Objectives Giant cell arteritis (GCA) is a complex systemic vasculitis mediated by the interplay between both genetic and epigenetic factors. Monocytes are crucial players of the inflammation occurring in GCA. Therefore, characterisation of the monocyte methylome and transcriptome in GCA would be helpful to better understand disease pathogenesis. Methods We performed an integrated epigenome-and transcriptome-wide association study in CD14+ monocytes from 82 patients with GCA, cross-sectionally classified into three different clinical statuses (active, in remission with or without glucocorticoid (GC) treatment), and 31 healthy controls. Results We identified a global methylation and gene expression dysregulation in GCA monocytes. Specifically, monocytes from active patients showed a more proinflammatory phenotype compared with healthy controls and patients in remission. In addition to inflammatory pathways known to be involved in active GCA, such as response to IL-6 and IL-1, we identified response to IL-11 as a new pathway potentially implicated in GCA. Furthermore, monocytes from patients in remission with treatment showed downregulation of genes involved in inflammatory processes as well as overexpression of GC receptor-target genes. Finally, we identified changes in DNA methylation correlating with alterations in expression levels of genes with a potential role in GCA pathogenesis, such as ITGA7 and CD63, as well as genes mediating the molecular response to GC, including FKBP5, ETS2, ZBTB16 and ADAMTS2. Conclusion Our results revealed profound alterations in the methylation and transcriptomic profiles of monocytes from GCA patients, uncovering novel genes and pathways involved in GCA pathogenesis and in the molecular response to GC treatment. |
| Ajuts: | European Commission 813545 Ministerio de Economía y Competitividad RD16/0012/0013 Instituto de Salud Carlos III CP17/00008 Agencia Estatal de Investigación IJC2019-040746-I |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | Annals of the rheumatic diseases, Vol. 81 Núm. 9 (january 2022) , p. 1290-1300, ISSN 1468-2060 |
