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Blood transcriptome indicates different disease etiology in pediatric ANCA-associated vasculitis subtypes.

ABSTRACT: Blood transcriptome indicates different disease etiology in pediatric ANCA-associated vasculitis subtypes.

PROVIDER: PRJNA532630 | ENA |

REPOSITORIES: ENA

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Blood transcriptome indicates different disease etiology in pediatric ANCA-associated vasculitis subtypes.

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.

2021-01-01 | GSE129752 | GEO

The effect of anti-MPO and anti-PR3 IgG from patients with ANCA vasculitis on human monocytes.

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.

2023-07-24 | GSE220695 | GEO

CC chemokine ligand 18 (CCL18) is associated with disease activity and relapse in ANCA-associated crescentic glomerulonephritis

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

Microarray analysis of peripheral blood mononuclear cells isolated from patients with ANCA-associated vasculitis and healthy controls

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

Shared molecular targets in the glomerular transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

Project description:Shared molecular targets in the glomerular transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

| PRJNA422459 | ENA

Shared molecular targets in the tubulointerstitial transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

Project description:Shared molecular targets in the tubulointerstitial transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

| PRJNA422468 | ENA

Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis.

Project description: Not available

| S-EPMC4587702 | biostudies-literature

Transcription profiling of human CD8 T cells in systemic lupus erythematosus (SLE) and vasculitis

Project description:Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of the potentially toxic immunosuppressive therapy required for their control. Clinically useful biomarkers have been identified using DNA microarrays in cancer but not autoimmunity. We show that transcriptional profiling of purified CD8 T cells, but not unseparated cells, identifies two distinct patient subgroups predicting long-term prognosis in two different autoimmune diseases, anti-neutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV) and systemic lupus erythematosus (SLE). We show that genes defining the poor prognostic group are enriched for genes of the IL7R pathway, TCR signalling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8 T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest novel potential therapeutic targets in autoimmunity.

2010-06-02 | E-MTAB-157 | biostudies-arrayexpress

The effect of MPO-ANCA on LPS-primed human monocytes

Project description:Human monocytes treated with LPS and MPO-ANCA or control IgG

2017-08-23 | GSE89153 | GEO

Shared molecular targets in the glomerular and tubulointerstitial transcriptomes from patients with nephrotic syndrome and ANCA-associated vasculitis

Project description:Shared molecular targets in the glomerular and tubulointerstitial transcriptomes from patients with nephrotic syndrome and ANCA-associated vasculitis

| PRJNA422466 | ENA

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