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Targeted RNA sequencing of archived giant cell arteritis temporal artery biopsies reveals viral signatures

ABSTRACT: Targeted RNA sequencing of archived giant cell arteritis temporal artery biopsies reveals viral signatures

PROVIDER: PRJNA731135 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14585700.fastq.gz	Fastqsanger.gz
	SRR14585701.fastq.gz	Fastqsanger.gz
	SRR14585702.fastq.gz	Fastqsanger.gz
	SRR14585703.fastq.gz	Fastqsanger.gz
	SRR14585704.fastq.gz	Fastqsanger.gz

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Temporal artery biopsy of Giant cell arteritis

Project description:Temporal artery biopsy of Giant cell arteritis

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Spatial profiling of temporal artery biopsies from patients with giant cell arteritis using NanoString GeoMx Whole Transcriptome Atlas

Project description:This study used the NanoString GeoMx Digital Spatial Profiler (DSP) platform to spatially profile gene expression in temporal artery biopsy tissue from patients with giant cell arteritis (GCA), taken at the time of diagnosis. Tissue sections were hybridised with the Human Whole Transcriptome Atlas panel and segmented to isolate immune-enriched (CD45⁺) and full-tissue regions across anatomical layers (adventitia, media, intima). Gene expression data were stratified according to clinical trajectory, comparing patients who later achieved sustained remission (SR) under glucocorticoid monotherapy with those who relapsed or failed to remit (non-remission, NR). Non-GCA controls (C) were also included for comparisons. Data from two sequencing batches were merged and normalised using DESeq2 for downstream analysis. This submission includes: (1) unnormalised digital counts and segment metadata; (2) normalised processed data and associated metadata; and (3) clinical information to aid re-analysis.

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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.

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Targeted RNA sequencing of archived giant cell arteritis temporal artery biopsies reveals viral signatures

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™).

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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

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Spatial profiling of temporal artery biopsies from patients with giant cell arteritis using NanoString GeoMx Whole Transcriptome Atlas

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

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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.

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

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

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