RT Journal Article
T1 Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids.
A1 Estupiñan-Moreno, Elkyn
A1 Ortiz-Fernandez, Lourdes
A1 Li, Tianlu
A1 Hernandez-Rodriguez, Jose
A1 Ciudad, Laura
A1 Andres-Leon, Eduardo
A1 Terron-Camero, Laura Carmen
A1 Prieto-Gonzalez, Sergio
A1 Espigol-Frigole. Georgina, 
A1 Cid, Maria Cinta
A1 Marquez, Ana
A1 Ballestar, Esteban
A1 Martin, Javier
K1 Giant Cell Arteritis
K1 Glucocorticoids
K1 Immune Complex Diseases
K1 Inflammation
AB 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. 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. 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. 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.
PB BMJ Group
YR 2022
FD 2022-05-17
LK http://hdl.handle.net/10668/20048
UL http://hdl.handle.net/10668/20048
LA en
NO Estupiñán-Moreno E, Ortiz-Fernández L, Li T, Hernández-Rodríguez J, Ciudad L, et al. Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids. Ann Rheum Dis. 2022 Aug 11;81(9):1290-1300.
NO This work was supported by the HELICAL Innovative Training Network,a European Commission funded project under the Horizon 2020 research andinnovation programme under the Marie Skłodowska-Curie grant agreementnumber 813 545 and, by the Cooperative Research Thematic Network programme(RD16/0012/0013). AM is recipient of a Miguel Servet fellowship (CP17/00008)from ISCIII (Spanish Ministry of Economy, Industry and Competitiveness). LO-F wassupported by Juan de la Cierva Incorporación fellowship (IJC2019-040746-I) funded by MCIN/AEI /10.13039/501100011033.
DS RISalud
RD Apr 9, 2025