Use of High-plex Data Provides Novel Insights into the Temporal Artery Processes of Giant Cell Arteritis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE237441 | GEO | 2023/08/24
REPOSITORIES: GEO
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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
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
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
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 | GSE201753 | GEO
Project description:CD4 T cells are important in GCA
2023-09-08 | GSE224527 | GEO
Project description:CD4 T cells are important in GCA
2023-09-08 | GSE224526 | GEO
Project description:Formalin-fixed, paraffin-embedded (FFPE) temporal artery sections from GCA subjects were stained for VZV antigen. Samples testing positive (VZV+) and negative (VZV-) from both GCA and control subjects without GCA were analyzed by targeted RNA sequencing of the whole-human transcriptome (BioSpyder TempO-Seq™).
2021-05-20 | GSE174694 | GEO
Project description:VCRC Longitudinal Protocol for Giant Cell Arteritis - VCRC 5502
| PRJNA198757 | ENA
Project description:There is a remodelling process which occurs in affected vessels during GCA and vascular smooth muscle cells are key cells in this process. Thickening of vessel might be responsible for vessel occlusion. We isolated vascular smooth muscle cells from temporal artery biopsies of patients with suspected GCA and used expression chips in order to identify genes up- and down-regulated in VSMC from patients with proven GCA compared to VSMC from patients with possible GCA and to VSMC from patients with another diagnosis.
2015-11-18 | GSE63425 | GEO
Project description:Background: Kawasaki Disease (KD) is a childhood illness of suspected infectious etiology that causes medium-sized muscular arteritis, most critically affecting the coronary arteries. No single diagnostic test exists, hampering early diagnosis and treatment. Approximately 25% of untreated patients develop coronary artery disease, and children who are treated with intravenous gammaglobulin but do not respond are also at high risk. Subacute/chronic arteritis and luminal myofibroblastic proliferation are the pathologic processes occurring in KD CA after the second week of illness, when neutrophilic necrotizing arteritis has subsided. The specific dysregulated immune pathways contributing to subacute/chronic arteritis have been unknown, hampering the development of effective immunomodulatory therapies for patients not responding to intravenous gammaglobulin therapy. Methods and Results: Deep RNA sequencing was performed on KD (n=8) and childhood control (n=7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Molecular pathways involving T helper cell, cytotoxic T lymphocyte, dendritic cells, and antigen presentation were the most significantly dysregulated. There was significant upregulation of immunoglobulin and type I interferon-stimulated genes. 80 upregulated extracellular genes encoding secreted proteins are candidate biomarkers of KD arteritis. Conclusions: The immune transcriptional profile in KD coronary artery tissues is primarily T helper and cytotoxic lymphocyte-mediated, and has features of an antiviral immune response such as type I interferon-stimulated gene expression. This first report of the KD coronary artery transcriptome identifies specific dysregulated immune response pathways that can inform the development of new therapies for and biomarkers of KD arteritis, and provide direction for future etiologic studies.
2016-04-22 | GSE64486 | GEO