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CTLA-4 pathway is instrumental in Giant Cell Arteritis

ABSTRACT: CTLA-4 pathway is instrumental in Giant Cell Arteritis

PROVIDER: PRJNA990713 | ENA |

REPOSITORIES: ENA

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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

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

Temporal artery biopsy of Giant cell arteritis

Project description:Temporal artery biopsy of Giant cell arteritis

| PRJNA1113976 | ENA

Temporal artery biopsy of Giant cell arteritis

Project description:Background Giant cell arteritis (GCA) is a prevalent, intractable, granulomatous, large-vessel vasculitis. The pathologic features include destruction of the tunica media, infiltrating macrophages and multinucleated giant cells (MNGCs), immune responses associated with CD4+ T cells, accumulation of myofibroblasts, and hypertrophy of the intima. Objectives The molecular pathology of GCA has largely remained elusive, while the morphological features are well defined. We aimed to identify key molecules associated with the pathogenesis of GCA. Method Arterial lesions were obtained through temporal artery biopsy from 16 patients, including those diagnosed as GCA and not. The obtained samples underwent genome-wide gene expression profiling. The resulting data were examined to reveal specific pathways and genes, and some of the molecules were followed up by immunohistochemistry. Results GCA lesions had a distinguishing pattern of gene expression, including enrichment of immune cells and phagocytic pathways related to microglia and osteoclasts. We found MMP12 (macrophage elastase), HLA-DRA, phagocytosis- and osteoclast-associated molecules in infiltrating macrophages and MNGCs. We also found LRRC15-expressing cells in the tunica intima, suggesting a myofibroblast subpopulation that suppresses cytotoxic CD8+ T cells. These molecules were often upregulated in other granulomatous diseases affecting not only arteries but also lymph nodes. Conclusion Infiltrating macrophages and MNGCs expressed molecules that contribute to the pathogenetic features of GCA, including degradation of the tunica medium, induction of immune responses, and accumulation of myofibroblasts. The extended list of key molecules provides a solid baseline of elucidating the pathogenesis of GCA and developing therapeutic strategies.

2025-05-07 | GSE267979 | GEO

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

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

| PRJNA934437 | ENA

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

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

| PRJNA934441 | ENA

VCRC Longitudinal Protocol for Giant Cell Arteritis - VCRC 5502

Project description:VCRC Longitudinal Protocol for Giant Cell Arteritis - VCRC 5502

| PRJNA198757 | ENA

Characterization of arterial dendritic cells in giant cell arteritis and polymyalgia rheumatica

Project description:Characterization of arterial dendritic cells in giant cell arteritis and polymyalgia rheumatica