Epigenome-wide association study of asthma remission in whole blood and nasal epithelium
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00010002026 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission.In this study, we hypothesized that epigenetic mechanisms may be involved in asthma remission.
| EGAS00001004766 | EGA
Project description: Not available
| S-EPMC7731549 | biostudies-literature
Project description:Identify biomarkers to predict response to therapy in polyarticular juvenile idiopathic arthritis (JIA) using gene expression microarrays. 42 samples from 13 controls, 14 active patients, 9 patients in clinical remission with medication (CRM), and 6 patients in clinical remission without medication (CR). All patients had polyarticular JIA.
2009-04-13 | E-GEOD-15645 | biostudies-arrayexpress
Project description:Background: Asthma, a complex chronic lung disease affecting the airways, has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A major goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omics signatures of asthma risk in the nasal epithelium focusing on populations of African ancestry. Methods: RNASeq data were generated from nasal epithelium in subjects recruited from up to 7 sites (Baltimore, Washington DC, Chicago, Denver, Salvador Brazil, Barbados, and Nigeria). Current asthma cases (N=253) were compared to never-asthma controls (N=283) to identify differentially expressed genes (DEGs; q <0.05). Network analyses were performed with Ingenuity Pathway Analysis (IPA; DEGs with q<0.05) and weighted gene co-expression network analysis (WGCNA; DEGs with q<0.15). All models were fully adjusted for ancestry, sampling site, and appropriate latent factors. Findings: CAAPA represents diversity across the African Diaspora with a wide range of continental African ancestry (9%-100%). We identified 389 DEGs; the top DEG, FN1, was downregulated in asthma cases (q=3.26x10-9) and encodes fibronectin which plays a role in wound healing. Others in the top 10 DEGs have high relevance for asthma: SNTG2 (q = 1.12x10-4) is the target of multiple miRNAs related to asthma; PPP1R9A expression (q=7.60x10-5) was previously determined to be influenced by IL-13 in mouse lung; and SPTBN1 (q=1.12x10-4) plays a key role in mediating TGFβ signaling. IPA revealed networks with upstream regulators relevant for immune response (IL4; p=7.25x10-10 and TGFβ1; p=5.47x10-8) and drug response (dexamethasone; p=4.31x10-10 and fluticasone propionate; p=9.42x10-8). Among asthma cases, genes regulated by dexamethasone and fluticasone propionate were not associated with inhaled corticosteroid medication use. The top three WGCNA modules implicate networks related to immune response (CEACAM5; p=9.62x10-16 and CPA3; p=2.39x10-14) and wound healing (FN1; p=7.63x10-9). Multi-omic analysis identified FKBP5 as a key contributor to asthma risk, whereby the association between nasal epithelium gene expression is mediated through methylation and is associated with increased use of inhaled corticosteroids. FKBP5 is a co-chaperone of glucocorticoid receptor signaling and known to be involved in drug response in asthma. Interpretation: Our analyses reveal genes and networks in asthma that are differentially expressed in nasal epithelium of asthma cases of African ancestry in CAAPA. Importantly, this work reveals molecular dysregulation on three axes – increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response – that may play a critical role in asthma within the African Diaspora.
2023-08-16 | GSE240567 | GEO
Project description:The study focus was differential methylation in bronchial biopsies between persistent asthma, asthma in remission and healthy controls using Illumina 450k arrays.
| EGAS00001003739 | EGA
Project description:Airway remodeling is a main pathological feature of asthma. The current therapy for asthma is mainly targeted for reducing inflammation, not particularly for airway remodeling. Herein, developing alternative and more effective therapy to attenuate remodeling is worthy of further study. Gu-Ben-Fang-Xiao Decoction (GBFXD) has been used to treat asthma for decades effectively and safely. In present study, GBFXD significantly regulated the airway inflammation, collagen deposition and the molecules relevant to airway remodeling such as Vimentin, α-SMA, hydroxyproline (HYP), and E-cadherin in chronic remission asthma (CRA) murine model. Subsequently, we found the overlapping differentially expressed proteins (DEPs) between Model/Control and GBFXD/Model mainly belonged to Collagen and Laminin which were extracellular matrix (ECM) proteins by iTRAQ proteomics. In addition, the KEGG analysis showed GBFXD could regulate pathways related to airway remodeling, such as ECM-receptor interaction, Focal adhesion, and PI3K/AKT signaling pathway which were top three pathways of most DEPs (Model/Control and GBFXD/Model) significantly enriched simultaneously. Further validation research showed GBFXD regulated Reticulon-4 (RTN4), thus suppressing the activation of PI3K/AKT pathway to alleviate the ECM proteins deposition. Thus, our findings indicate GBFXD regulate the PI3K/AKT pathway via RTN4 to improve airway remodeling and provide a new insight into the molecular mechanism of GBFXD for treating CRA.
2021-09-09 | PXD020711 | Pride
Project description:The study focus was differential expression in bronchial biopsies between persistent asthma, asthma in remission and healthy controls using RNAseq.
| EGAS00001003735 | EGA
Project description:Background: Nasal epithelia are emerging as a proxy measure of gene expression of the airway epithelium in asthma. We hypothesized that epigenetic marks regulate gene expression of the nasal epithelia and consequently may provide a novel target for allergic asthma. Methods: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma [N=36] versus healthy controls [N=36]. Results were validated in an independent population of asthmatics [N=30]. Results: We identified 186 genes with significant methylation changes, either as regions (differentially methylated regions [DMRs]) or single CpGs (differentially methylated probes [DMPs]) after adjustment for age, gender, race/ethnicity, batch effects, inflation, and multiple comparisons (false discovery rate-adjusted q<0.05). Genes differentially methylated include those with established roles in asthma and atopy, components of the extracellular matrix, genes related to immunity, cell adhesion, epigenetic regulation, and airway obstruction. The methylation changes are large (median 9.5%, range: 2.6-29.5% methylation change) and similar in magnitude to those observed in malignancies. Hypo- and hyper-methylated genes were associated with increased and decreased gene expression respectively (P<2.8x10-6 for DMRs and P<7.8x10-10 for DMPs). Quantitative analysis of methylation-expression relationships in 53 differentially expressed genes demonstrated that 32 (60%) have significant (q<0.05) methylation-expression relationships within 5kb of the gene. 10 loci selected based on the relevance to asthma, magnitude of methylation change, and asthma specific methylation-expression relationships were validated in an independent cohort of children with asthma. Conclusions: Our findings that epigenetic marks in respiratory epithelia are associated with allergic asthma in inner-city children provide new targets for biomarker development, and novel approaches to understanding disease pathogenesis. case control design with nasal epithelial cells from 36 atopic asthmatic and 36 nonatopic nonasthmatic children from the inner city
2015-11-01 | E-GEOD-65163 | biostudies-arrayexpress
Project description:The majority of common chronic human diseases remain incurable, impacting a significant portion of the population and necessitating lifelong treatments that impose a substantial burden on health, the economy, and society. Asthma, the most prevalent respiratory disease, exemplifies this challenge, affecting over 300 million people and causing more than 250,000 deaths annually. Here, we demonstrate the achievement of long-term remission of type 2-high asthma through a single infusion of engineered CAR T cells. By utilizing IL-5 as the targeting domain and depleting BCOR and ZC3H12A, we engineer long-lived CAR T cells designed to eradicate IL-5R+ eosinophils, termed Immortal-like and Functional IL-5 CAR T (5TIF) cells. Furthermore, we enhance 5TIF cells by engineering them to secrete an IL-4 mutein that blocks the signaling of both IL-4 and IL-13, two inflammatory cytokines driving asthma pathology, resulting in the creation of 5TIF4 cells. In multiple asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, leads to long-term depletion of pathological eosinophils and blockade of IL-4/IL-13 actions. This results in sustained repression of type 2 inflammation and alleviation of asthmatic symptoms. Additionally, 5TIF4 cells can be induced in human T cells in NSG mice. These findings demonstrate that asthma, a prevalent and incurable disease, can undergo durable remission through a single infusion of engineered CAR T cells. This breakthrough paves the way for the potential functional cure of chronic noncancerous diseases using long-lived CAR T cells.
2024-04-04 | GSE262360 | GEO
Project description:The majority of common chronic human diseases remain incurable, impacting a significant portion of the population and necessitating lifelong treatments that impose a substantial burden on health, the economy, and society. Asthma, the most prevalent respiratory disease, exemplifies this challenge, affecting over 300 million people and causing more than 250,000 deaths annually. Here, we demonstrate the achievement of long-term remission of type 2-high asthma through a single infusion of engineered CAR T cells. By utilizing IL-5 as the targeting domain and depleting BCOR and ZC3H12A, we engineer long-lived CAR T cells designed to eradicate IL-5R+ eosinophils, termed Immortal-like and Functional IL-5 CAR T (5TIF) cells. Furthermore, we enhance 5TIF cells by engineering them to secrete an IL-4 mutein that blocks the signaling of both IL-4 and IL-13, two inflammatory cytokines driving asthma pathology, resulting in the creation of 5TIF4 cells. In multiple asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, leads to long-term depletion of pathological eosinophils and blockade of IL-4/IL-13 actions. This results in sustained repression of type 2 inflammation and alleviation of asthmatic symptoms. Additionally, 5TIF4 cells can be induced in human T cells in NSG mice. These findings demonstrate that asthma, a prevalent and incurable disease, can undergo durable remission through a single infusion of engineered CAR T cells. This breakthrough paves the way for the potential functional cure of chronic noncancerous diseases using long-lived CAR T cells.
2024-04-04 | GSE262359 | GEO