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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

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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.

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

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