The effect of anti-MPO and anti-PR3 IgG from patients with ANCA vasculitis on human monocytes.
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ABSTRACT:
PROVIDER: PRJNA911181 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22684700_1.fastq.gz | Fastqsanger.gz | |||
| SRR22684700_2.fastq.gz | Fastqsanger.gz | |||
| SRR22684800_1.fastq.gz | Fastqsanger.gz | |||
| SRR22684800_2.fastq.gz | Fastqsanger.gz | |||
| SRR22684701_1.fastq.gz | Fastqsanger.gz |
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Project description:These data are part of a body of work exploring the effect of IgG from patients with ANCA vasculitis on human monocytes in vitro. Please see the relevant publication for a full description.
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Project description:Patients with anti-MPO vasculitis have increased serum levels of the signalling molecule cGAMP suggestive of ongoing DNA recognition by the cGAS/STING pathway. Consistent with this gene set enrichment analysis of peripheral blood mononuclear cell transcriptomes from patients with active anti-MPO vasculitis revealed up-regulation of type 1 interferon response genes compared to healthy controls.
2022-08-19 | E-MTAB-12008 | biostudies-arrayexpress
Project description:To study monocyte and macrophage activation in ANCA-associtated vasculitis (AAV), we performed bulk RNA sequencing of bead-selected monocytes and in vitro cultured monocyte-derived macrophages from AAV patients and healthy controls. Overview patients included for sequencing monocytes: - AAV active disease, n=4, MPO-AAV=4 - AAV remission, n=10, PR3-AAV=5, MPO-AAV=5 - Healthy controls, n=6 Overview patients included for sequencing monocyte-derived macrophages: - AAV active, n=1, PR3-AAV=1 - AAV remission, n=3, PR3-AAV=3 - Healthy controls, n=3
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Project description:Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic and refractory disease, characterized by necrotizing small to medium vessel vasculitides. AAV constitutes three distinct disorders: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) (formerly known as Wegener's granulomatosis), and eosinophilic granulomatosis with polyangiitis (EGPA) (formerly known as Churg-Strauss syndrome). ANCA, a characteristic autoantibody for AAV consists of two major subtypes: one against myeloperoxidase (MPO-ANCA) and the other against leukocyte proteinase 3 (PR3-ANCA). MPO-ANCA is mainly detected in patients with MPA (55-90%) and in those with EGPA (20-40%) and less frequently detected in patients with GPA (20-30%). We hypothesized that an aberrant PTM occurred in neutrophil MPO in patients with MPO-ANCA-positive AAV (MPO-AAV) is involved in the production of MPO-ANCA. To test the hypothesis, SWATH-MS was used to comprehensively quantify PTMs of human MPO purified from neutrophils of MPO-AAV and healthy controls, and PTMs of mouse MPO treated with hydrogen peroxide in vitro.
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Project description:Purpose: The goal of this study was to compare gene expression profiles from whole blood RNA-Seq data from pediatric ANCA-associated vasculitis patients to identify mechanistic endotypes. Methods: Whole blood mRNA profiles were generated from pediatric and adult vasculitis patients using Illumina GAIIx or Hi Seq 2500 RNA-Seq. Fastq files were alinged to human genome version GRC38.91 using STAR v2.6 and count data was generated with HTSEQ v0.61p1. Counts that passed quality and minimum expression filteres were anlayzed by hierarchical clustering based on Euclidean distance, and then for differential expression with DESeq2. Results: Our workflow identified 14,156 transcripts consistently expressed in vasculitis patients. Distance hierarchcial clustering identified three groups within these pediatric samples, and two groups plus one outlier in the adult samples. The two largest pediatric clusters were used as groups for differential expression analysis with the DESeq2 package for R. DE analysis identified 3,809 differentially expressed genes between clusters. Between the two adult groups, 1,682 genes were differentially expressed. DE genes were anlayzed for enrichment using ReatomePA as the reference database. This analysis revealed that genes involved in T-cell mediated immunity are more highly expressed in pediatric patients that fell into one endotype and those involved in neutrophil and Toll-like receptor mediated inflammation are more highly expressed in pediatric patients that fell into the other endotype group. Similar results were also seen in adults. Conclusions: This study utilizes RNA-Seq data to investigate the etiologies of ANCA-associated vasculitis. Using this approach we have identified T-cell mediated immunity and Toll-like receptor mediated inflammation as potentially differing inflammatory mechanisms in both pediatric and adult vasculitis patients that do not fall along normal diagnostic criteria.
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Project description:Anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis is the most frequent cause of crescentic glomerulonephritis. Histopathologic features and clinical course of the disease are diverse and judgment of disease activity is often limited due to the lack of reliable activity markers. In order to define potentially new molecular or cellular markers in the kidney which may predict clinical outcome, we performed microarray analyses of renal biopsies from patients with ANCA-associated crescentic glomerulonephritis. We correlated expression profiles with clinical data from our prospective study of patients with renal ANCA disease. The CC chemokine ligand 18 (CCL18) was one of the most up-regulated proteins in kidneys of patients with ANCA-associated crescentic glomerulonephritis. CCL18 producing cells in the kidneys were identified as CD68 and CD209 positive myeloid dendritic cells. The density of CCL18 positive cells correlated with the severity of acute tubular injury and with the impairment of renal function. CCL18 protein levels were elevated in serum samples of patients with renal ANCA disease when compared with patients with non- ANCA-associated crescentic glomerulonephritis. Persistence of high CCL18 serum levels correlated with impairment of renal function and the risk of relapsing disease. Therefore, CCL18 might serve as a marker for persistent disease activity and renal relapses in ANCA-associated vasculitis.
2015-09-03 | E-MTAB-1944 | biostudies-arrayexpress
Project description:Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is a life-threatening systemic autoimmune disease that frequently presents as crescentic glomerulonephritis (GN) leading to kidney failure1. Despite recent advances2, treatment for most patients with ANCA-associated GN relies on unspecific immunosuppressive agents that are hazardous and only partially efficacious. To develop an anti-T-cell cytokine treatment strategy based on the immunopathogenesis of the individual patient, we established the combination of rapid single-cell immune profiling with standard histopathological analyses of renal biopsies. We report two patients with biopsy-proven ANCA-associated GN who presented with renal failure and active urinary sediment despite immunosuppressive therapy. Our data suggest that the integration of single-cell immune profiling with clinical and histopathological information facilitates personalized anti-cytokine therapies, such as ustekinumab in ANCA-GN, and warrants further investigation.
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