Nasal DNA methylation differentiates corticosteroid treatment response in pediatric asthma: A pilot study
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE104087 | GEO | 2017/10/23
SECONDARY ACCESSION(S): PRJNA408173
REPOSITORIES: GEO
Similar Datasets
Project description:Background: A subset of asthmatics does not respond to steroid therapy and therefore is at risk for escalation of disease severity. The cause of corticosteroid resistant (CR) asthma is unknown. Gene microarray technologies have the potential to substantiate new hypotheses regarding the etiology of corticosteroid resistance. Methods: Gene microarray analysis was performed with bronchoalveolar lavage (BAL) cells of CR and corticosteroid sensitive (CS) asthmatics. Increased gene expression was verified with real time PCR and at the protein level by ELISA. Findings: Microarray analyses demonstrated significantly higher levels (over two-fold increase, p<0.05) of TNF-alpha, IL-1alpha, IL-1beta, IL-6, CXCL1, CXCL2, CXCL3, CXCL8 (IL-8), CCL3, CCL4, CCL20 gene expression in BAL cells of CR than CS asthmatics. These findings, confirmed by RT-PCR in additional BAL samples, were consistent with classical macrophage activation by bacterial products. In contrast, markers of alternatively-activated macrophages, Arginase I and CCL24, were decreased in CR asthmatics. Genes associated with activation of the LPS signaling pathway (EGR1, DUSP2, MAIL, TNFAIP3) were significantly elevated in CR BAL samples (p<0.05). CR asthmatics had significantly higher amounts (1444.0±457.3 pg per mg of total protein) of LPS in BAL fluid than CS asthmatics (270.5±216.0 pg; p<0.05). Prolonged exposure to LPS induced functional steroid resistance to dexamethasone (DEX) in normal monocytes, demonstrated by persistently elevated IL-6 levels in the presence of DEX. Interpretation: Classical macrophage activation and induction of LPS signaling pathways along with high endotoxin levels detected in BAL fluid from CR asthmatics suggest that LPS exposure may contribute to CR asthma. Keywords: Disease state analysis
2009-06-22 | GSE7368 | GEO
Project description:Nasal DNA methylation differentiates corticosteroid treatment response in pediatric asthma: A pilot study
| PRJNA408173 | ENA
Project description:Background: A subset of asthmatics does not respond to steroid therapy and therefore is at risk for escalation of disease severity. The cause of corticosteroid resistant (CR) asthma is unknown. Gene microarray technologies have the potential to substantiate new hypotheses regarding the etiology of corticosteroid resistance. Methods: Gene microarray analysis was performed with bronchoalveolar lavage (BAL) cells of CR and corticosteroid sensitive (CS) asthmatics. Increased gene expression was verified with real time PCR and at the protein level by ELISA. Findings: Microarray analyses demonstrated significantly higher levels (over two-fold increase, p<0.05) of TNF-alpha, IL-1alpha, IL-1beta, IL-6, CXCL1, CXCL2, CXCL3, CXCL8 (IL-8), CCL3, CCL4, CCL20 gene expression in BAL cells of CR than CS asthmatics. These findings, confirmed by RT-PCR in additional BAL samples, were consistent with classical macrophage activation by bacterial products. In contrast, markers of alternatively-activated macrophages, Arginase I and CCL24, were decreased in CR asthmatics. Genes associated with activation of the LPS signaling pathway (EGR1, DUSP2, MAIL, TNFAIP3) were significantly elevated in CR BAL samples (p<0.05). CR asthmatics had significantly higher amounts (1444.0±457.3 pg per mg of total protein) of LPS in BAL fluid than CS asthmatics (270.5±216.0 pg; p<0.05). Prolonged exposure to LPS induced functional steroid resistance to dexamethasone (DEX) in normal monocytes, demonstrated by persistently elevated IL-6 levels in the presence of DEX. Interpretation: Classical macrophage activation and induction of LPS signaling pathways along with high endotoxin levels detected in BAL fluid from CR asthmatics suggest that LPS exposure may contribute to CR asthma. Experiment Overall Design: Patients with a diagnosis of asthma according to American Thoracic Society criteria were selected for evaluation. Asthmatics had a baseline FEV1% predicted of 55% to 85% of predicted, a beta2-adrenergic response of â¥12% of baseline FEV1% predicted and/or a methacholine PC20 value of â¤8 mg/ml. Asthma patients were further subdivided in CR and CS groups, based on their response to steroids. The definition was based on change in FEV1 % predicted over a one-week course of 40 mg/day of oral prednisone. Asthmatic patients were defined as CS if they had an increase in FEV1% predicted of greater than 15% after a one-week course of prednisone, and as CR if less than 12% change in FEV1% predicted was observed. None of the asthmatic subjects recruited for this study had evidence for other types of lung diseases. None of the subjects had received systemic corticosteroid therapy for at least one month prior to bronchoscopy. All subjects provided written informed consent to participate in the study. The study was approved by the Institutional Review Board at National Jewish Medical and Research Center, Denver, CO. Gene array studies of BAL macrophages were performed in 3 CR and 3 CS asthmatics.
2009-07-01 | E-GEOD-7368 | biostudies-arrayexpress
Project description:Rationale: DNA methylation plays a critical role in asthma development, but differences in DNA methylation associated with asthma severity, especially among adults, are less well-defined. Changes in DNA methylation are influenced by exposure to air pollution, which is a risk factor for asthma exacerbation and severity. Here, we examined how DNA methylomic patterns in adult asthmatics differ by asthma severity and exposure to different components of air pollution. Methods: Peripheral blood CD3+ T cells from adult asthmatics in Beijing, China were serially collected from 37 patients (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Measurements and Main Results: Significant differences in DNA methylation were noted among subjects with different degrees of asthma severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume, and asthma control test scores. Differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function, and included gene ontology categories related to cellular adhesion, developmental pathways, and calcium signaling. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, PDGFRA, CDH1, CAV1, and NOTCH4. Differences in DNA methylation also varied by exposure to ambient air pollution, with different components of pollution effecting methylation of different groups of genes. Conclusion: These findings demonstrate how adult asthmatics possess widespread differences in the DNA methylation that associated with varying asthma severity and how air pollution might contribute to more severe asthma via changes in DNA methylation.
2024-07-31 | GSE226257 | GEO
Project description:Background: Treatment response to systemic corticosteroid in asthmatic children is heterogeneous and may be mediated by epigenetic mechanism(s). We aim to identify DNA methylation (DNAm) changes responsive to steroid, and DNAm biomarkers that distinguish treatment response.Materials and methods: We followed 33 children (ages 5-18) presenting to the Emergency Department (ED) for asthma exacerbation. Based on whether they met discharge criteria in ?24 hours, participants were grouped into good and poor responders to steroid treatment. Nasal samples were collected upon presentation to the ED (T0) and 18-24 hours later (T1). Genome-wide DNAm was measured for both time points in 20 subjects, and compared between T0 and T1 in good and poor responders respectively. DNAm at T1 was also compared between two responder groups. DNAm of selected CpGs was verified in the complete cohort, and expression of associated genes was examined. Interactions between DNAm, common single nucleotide polymorphism (SNP) located at the CpG sites and treatment responses were assessed.Results: Three CpGs located in the OTX2 promoter showed responder-specific DNAm changes from T0 to T1, in which DNAm decreased in good but not in poor responders. Good and poor responders showed differential DNAm at T1 in 127 CpGs without and 182 CpGs with common SNP co-localization. Negative correlations between DNAm and gene expression were observed at CpGs located within the LDHC promoter, suggesting an impact of DNAm on gene regulation. Interactions between SNPs, DNAm and treatment response were detected.Conclusion: Acute systemic steroid treatment modifies nasal DNAm in good responders. Nasal DNAm, dependent or independent of SNPs, can differentiate response to treatment in acute asthmatic children.
| S-EPMC5640236 | biostudies-literature
Project description:Mouse DNA methylation atlas using Infinium Mouse Methylation Beadchips
| PRJNA764585 | ENA
Project description:The exacerbation of disease in asthmatics has been linked to both exposure to environmental agents as well as to the presence of virus in airways, particularly rhinovirus. The hypothesis tested in these experiments is that differences in gene expression profiles in epithelial cells derived from asthmatic and normal airways can be linked to enhanced responsiveness of the epithelium in its pro-inflammatory, immulogic or other activities that may lead to the exacerbation of disease.
2007-12-12 | E-GEOD-470 | biostudies-arrayexpress
Project description:DNA methylation in asthmatics after short-term exposure to diesel exhaust
2014-04-08 | GSE56553 | GEO
Project description:The heterogeneity of asthma has prompted attempts at classifications based on clinical phenotypes and cluster designations. Although helpful, reliance on clinical parameters fails to address fundamental issues resulting in specific phenotypes, in particular, steroid-resistant (SR) asthma. Limited data are available defining the mechanisms or pathways (endotypes) causing the failure of inhaled corticosteroids (ICS) in SR asthmatics. Unlike CD4+ T cells, both human and mouse CD8+ T cells fail to undergo apoptosis in the presence of corticosteroids (CS) positioning them as unique effector cells. Whole transcriptome analyses of peripheral CD8+ T cells from steroid-sensitive or steroid-resistant asthmatics or healthy controls on days 0 and 8 were performed.
2017-10-08 | GSE100624 | GEO
Project description:DNA methylation classification reference set (1077) and validation set (428) of 1505 sarcoma samples using Illumina HumanMethylation450 BeadChips or Illumina Infinium HumanMethylation850 BeadChips
2020-03-01 | GSE140686 | GEO