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Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids [array]

ABSTRACT: Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids [array]

PROVIDER: PRJNA832872 | ENA |

REPOSITORIES: ENA

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Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids [array]

Project description: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, characterization 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 status (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 pro-inflammatory 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 interleukin (IL)-6 and IL-1, we identified a significant number of chemokines, such as CCRL2, and integrins. 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.

2022-06-28 | GSE201752 | GEO

Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids [RNA-Seq]

2022-06-28 | GSE201753 | GEO

Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids

Project description:Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids

| PRJNA832864 | ENA

Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids [RNA-Seq]

Project description:Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids [RNA-Seq]

| PRJNA832873 | ENA

Use of High-plex Data Provides Novel Insights into the Temporal Artery Processes of Giant Cell Arteritis

Project description:To identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls

2023-08-24 | GSE237441 | GEO

Single-cell RNA sequencing on peripheral blood cells of patients with giant cell arteritis

Project description:Vasculitis is characterized by the inflammation of blood vessels. In patients with giant cell arteritis (GCA) large- to medium-sized vessels are affected. Single-cell RNA sequencing was performed on GCA patients and healthy controls (HC) to study the transcriptome of peripheral blood mononuclear cells of patients and controls.

2022-03-22 | GSE198891 | GEO

CD4 T cells in Giant Cell Arteritis

Project description:CD4 T cells in Giant Cell Arteritis

| PRJNA931599 | ENA

CTLA-4 pathway is instrumental in Giant Cell Arteritis

Project description:BACKGROUND: Giant Cell Arteritis (GCA) causes severe inflammation of the aorta and its branches and is characterized by intense effector T cells infiltration. The roles that immune checkpoints play in pathogenesis of GCA are still unclear.Our aim was to study the immune checkpoints interplay in GCA. METHODS: First, we used VigiBase, the WHO international pharmacovigilance database, to evaluate the relationship between GCA occurrence and immune checkpoint inhibitors (ICI) treatments. We then further dissected the role of ICI in the pathogenesis of GCA, using immunohistochemistry, immunofluorescence, transcriptomics and flow cytometry on peripheral blood mononuclear cells (PBMCs) and aortic tissues of GCA patients and appropriated controls. RESULTS: Using VigiBase, we identified GCA as a significant immune related adverse event associated with anti-CTLA-4 (Cytotoxic T-lymphocyte-associated-protein-4) but not anti-PD-1/PD-L1 treatment. We further dissected a critical role for CTLA-4 pathway in GCA by identification of the dysregulation of CTLA-4-derived gene pathways and proteins in CD4+ T cells (and specifically Tregs) present in blood and aorta of GCA patients versus controls. While Tregs were less abundant and activated/suppressive in blood and aorta of GCA versus controls, they still specifically upregulated CTLA-4. Activated and proliferating CTLA-4+ Ki-67+ Tregs from GCA were more sensitive to anti-CTLA-4 (Ipilimumab)-mediated in vitro depletion versus controls. CONCLUSIONS: We highlighted the instrumental role of CTLA-4 immune checkpoint in GCA which provides a strong rationale for targeting this pathway.

2023-07-03 | GSE236367 | GEO

Methylome and transcriptome profiling of giant cell arteritis monocytes reveals novel pathways involved in disease pathogenesis and molecular response to glucocorticoids

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-28 | GSE201754 | GEO

CD4 T cells in Giant Cell Arteritis (scRNA-Seq)

Project description:CD4 T cells in Giant Cell Arteritis (scRNA-Seq)

| PRJNA934441 | ENA