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Defining the Nasal Transcriptome in Granulomatosis with Polyangiitis

ABSTRACT: Defining the Nasal Transcriptome in Granulomatosis with Polyangiitis

PROVIDER: PRJNA488242 | ENA |

REPOSITORIES: ENA

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Defining the Nasal Transcriptome in Granulomatosis with Polyangiitis

Project description:Objectives: To determine whether disease processes related to granulomatosis with polyangiitis (GPA) are reflected in gene expression profiles of nasal mucosa. Methods: Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators. Results: 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change > 1.5; false discovery rate < 0.05). Top canonical pathways upregulated in nasal brushings from patients with GPA include granulocyte adhesion and diapedesis (p=8.6 E-22), agranulocyte adhesion and diapedesis (p=1.3 E-14), interleukin 10 signaling (3.0 E-11), and TREM1 signaling (9.0 E-11). A set of genes differentially expressed in GPA independent of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g. osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease. Conclusions: Profiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Airway-based expression profiling is feasible and informative in GPA.

2018-08-29 | GSE119136 | GEO

miRNA profiling of Regulatory T-cells of patients with Granulomatosis with PolyAngiitis (GPA) in Remission versus Healthy Controls

Project description:Regulatory T cells (Tregs) are frequently functionally impaired in patients with Granulomatosis with PolyAngiitis (GPA). However, the mechanism underlying their impaired function is unknown. Here, we hypothesized that Treg dysfunction in GPA is due to altered microRNA (miRNA) expression.

2019-09-30 | E-MTAB-8282 | biostudies-arrayexpress

Defining the nasal transcriptome in granulomatosis with polyangiitis (Wegener's).

Project description: Not available

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VCRC Longitudinal Protocol for Granulomatosis with Polyangiitis (Wegener's) and Microscopic Polyangiitis - VCRC 5505

Project description:VCRC Longitudinal Protocol for Granulomatosis with Polyangiitis (Wegener's) and Microscopic Polyangiitis - VCRC 5505

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Pulmonary Eosinophilic Granulomatosis with Polyangiitis has IgG4 Plasma Cells and Immunoregulatory Features

Project description:The pathologic findings and immunologic mechanisms in eosinophilic granulomatosis with polyangiitis (EGPA) are poorly understood. To characterize pulmonary EGPA’s mechanisms, we examined EGPA paraffin-embedded lung biopsies by immunostaining, RNA sequencing, and reverse transcriptase PCR, compared to normal lung. EGPA lung infiltrates had eosinophils, alveolar macrophages, B and T cells, plasma cells, basophils, and mast cells. Mast cell degranulation was sparse. PhosphoSMAD2 immunostaining suggests TGFβ activity. Using both immunostaining and RNA-sequencing, showed significant increases for both type 2 related genes (CD209, TNFSF14 (induces TGFβ and IL-13)), immunoregulatory genes (FOXP3, CYP27B1 (makes calcitriol), ALOX15 and particularly IGHG4). Regulatory T cells and IgG4 plasma cells with IgG4-containing presumed immune complexes coating macrophages, were strikingly abundant relative to controls. HPGD (metabolizes prostaglandins and other eicosanoids) was substantially decreased. RNA studies also showed increased contents of collagen transcripts, IL13, CCL18, and CCL13. These findings suggest a novel mechanism involving alveolar macrophages, activated by ALOX15-eicosanoid products, making chemokines CCL18 and CCL13 and thus inducing a mixed type 2 plus immunoregulatory immune response. This infiltrate resembles the immune response to an invasive parasite rather than the IgE / mast cell degranulation response to luminal parasites or in asthma and other classic allergies. These findings also suggest new potential treatment targets for EGPA.

2020-01-28 | GSE144302 | GEO

Pulmonary Eosinophilic Granulomatosis with Polyangiitis has IgG4 Plasma Cells and Immunoregulatory Features

Project description:Pulmonary Eosinophilic Granulomatosis with Polyangiitis has IgG4 Plasma Cells and Immunoregulatory Features

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Gene expression profile of CD4+ T lymphocytes from patients with eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome

Project description:Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare and heterogeneous disease of unknown etiology, classified among ANCA-associated vasculitis, with an insatisfactory response to treatment. The aims of the current project are: 1) To investigate pathogenic pathways involved in EGPA that could be potentially druggable or provide clinically useful biomarkers by a cross-sectional study determining gene-expression profile of peripheral blood CD4+T lymphocytes in clinically stable patients with EGPA, patients with asthma and healthy controls. By using gene set expression analysis (GSEA) we will identify the main differentially expressed pathways. The most signficant differentially expressed transcripts will be validated as potential biomarkers by quantitative real time RT-PCR and by serum ELISA if encoding for a soluble product in an additional cohort. 2) To determine the heterogeneity of the EGPA by analyzing its transcriptome according to subgroups of patients defined by clinical variables and response to treatment. If we obtain significant differentially expressed genes for each category defined by clinical variables, these genes will be also validated in an additional cohort. 3) Moreover, an unsurpervised clustering analysis will be performed in order to identify non-predefined subtypes. With this study, we aim to contribute to the characterization of the molecular basis of the heterogeneity of EGPA patients and to identify pathways potentially involved in disease pathogenesis.

2025-12-15 | E-MTAB-16277 | biostudies-arrayexpress

Transcriptome analysis of naive CD4T cells from Granulomatosis with Polyangiitis(GPA) patients and healthy control (HC)

Project description:Transcriptome analysis of naive CD4T cells from Granulomatosis with Polyangiitis(GPA) patients and healthy control (HC)

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Single-Cell Multi-Omics Reveals Activation of the STAT3–PIM1 Axis in T Cell Subsets in Proteinase 3-ANCA-Positive Granulomatosis with Polyangiitis

Project description:Granulomatosis with polyangiitis (GPA) is an autoimmune disease marked by relapses and treatment-related morbidity. CD4⁺ T cells play a central role in GPA pathogenesis, but their molecular profile remains incompletely defined. This study aimed to characterize CD4⁺ T cells in proteinase 3-ANCA-positive GPA (PR3-GPA) patients using single-cell multi-omics to identify molecular signatures associated with disease activity. Peripheral blood mononuclear cells were obtained from PR3-GPA patients during active disease, remission, and healthy controls. Single-cell RNA sequencing and CITE-seq were used to define transcriptional and protein expression profiles of CD4⁺ T cell subsets. Findings were validated using RT-qPCR, flow cytometry–based assays, including phospho-flow cytometry, and in vitro inhibition assay. scRNA-seq and CITE-seq revealed upregulated PIM1 expression in CD4⁺ T cell subsets in active GPA compared to controls. Pim kinase inhibition reduced CD4⁺ T cell activation, proliferation, and cytokine production. These findings indicate that circulating CD4⁺ T cells in active PR3-GPA are characterized by activation of the STAT3–PIM1 axis, potentially driven by upstream IL-6 signaling.

2026-05-25 | GSE331351 | GEO

Exploring the microbiota pecularity in stool and biopsies of Eosinophilic Granulomatosis with Polyangiitis (EGPA) patients

Project description:Exploring the microbiota pecularity in stool and biopsies of Eosinophilic Granulomatosis with Polyangiitis (EGPA) patients

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