Transcriptomic profiling of CD8+ T cells from steroid-sensitive and steroid-resistant asthmatics and healthy controls
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE100624 | GEO | 2017/10/08
SECONDARY ACCESSION(S): PRJNA392314
REPOSITORIES: GEO
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Project description:We performed small RNA sequencing (TruSeq) of gene expression on bronchial cells from human bronchial epithelial brushings from 16 independent subjects whose samples were classified as either healthy controls (with no asthma or lung disease) or steroid-naive asthmatics (subjects with asthma not using inhaled corticosteroids (ICS) for 6 weeks before enrollment that were studied at baseline ('Steroid-naive asthma - Baseline') or after 8 weeks of treatment with budesonide, 200 μg twice a day, ('Steroid-naive asthma - Post-ICS treatment')). The goal was to assess abundance of miRNAs in all the samples collectively.
2021-01-01 | GSE164119 | GEO
Project description:Background: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. Methods: Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS-), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. Results: AsResults: As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic. a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.
2021-07-15 | GSE179156 | GEO
Project description:To better understand the therapeutic potential of targeting Th2 inflammation in asthma, we performed genome-wide expression profiling of endobronchial biopsies in asthmatics and healthy controls stratified according a previously defined three-gene Th2 signature in bronchial epithelium. The Th2 signature is defined as relatively high expression of POSTN, CLCA1, and SERPINB2.
2011-01-18 | GSE23611 | GEO
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:Gene expression profiling was performed on sputum samples obtained from asthmatics and matched healthy controls, to identify markers associated with various asthma subtypes. Sputum samples were collected from asthmatics and healthy controls and subjected to expression profiling using Affymetrix HG-U133Plus2.0 microarrays.
2015-10-23 | E-GEOD-41863 | biostudies-arrayexpress
Project description:Gene expression profiling was performed on sputum samples obtained from asthmatics and matched healthy controls, to identify markers associated with various asthma subtypes.
2015-10-23 | GSE41863 | GEO
Project description:Gene expression profiling was performed on nasal scrape samples obtained from asthmatics and matched healthy controls, to identify markers associated with various asthma subtypes. Nasal scrape samples were collected from asthmatics and healthy controls and subjected to expression profiling using Affymetrix HG-U133Plus2.0 microarrays.
2015-10-23 | E-GEOD-41862 | biostudies-arrayexpress
Project description:Gene expression profiling was performed on nasal scrape samples obtained from asthmatics and matched healthy controls, to identify markers associated with various asthma subtypes.
2015-10-23 | GSE41862 | GEO
Project description:Background: Around 5% of children with asthma suffer from chronic symptoms and/or severe exacerbations despite extensive treatment. The causes of severe therapy-resistant childhood asthma are poorly understood. Objectives: To define global patterns of gene expression in severe therapy-resistant vs. controlled asthma and healthy controls. Methods: Children with severe, therapy-resistant (SA, n=20) and controlled asthma (CA, n=20) were identified from a Swedish nation-wide study including extensive clinical and immunological characterisation. In addition, healthy controls were recruited (Ctrl, n=19). White blood cells were isolated and the global transcriptome profile was characterised using the Affymetrix Human Gene ST 1.0 chip. Results: 1378 genes were differentially expressed in one or several of the CA vs. Ctrl, SA vs. CA or SA vs. Ctrl contrasts. A large number could uniquely differentiate the SA group from the CA (n=351 genes) and Ctrl (n=315) groups, whereas fewer genes differentiated the CA from the Ctrl group (n=149). Several non-coding RNAs were found up-regulated in SA compared to CA or Ctrl. Three significantly enriched KEGG pathways were represented; bitter taste transduction, TAS2Rs (up-regulated mostly in SA), natural killer cell mediated cytotoxicity (up-regulated in CA) and N-Glycan biosynthesis (down-regulated in SA). An unsupervised hierarchical clustering of the 1378 genes could crudely separate the SA, CA and Ctrl individuals. Conclusion: Our data indicate a separation in gene expression patterns between children with severe, therapy-resistant asthma and controlled persistent asthma, and suggest novel pathways characterizing the severe therapy-resistant asthma phenotype. The transcriptomes of 59 subjects were assayed on the Affymetrix Human Gene ST 1.0 expression array. All samples passed pre-hybridisation quality control. After pre-processing and quality control of the post-hybridised arrays, five samples were regarded as outliers and removed (ctrl 510, MA 248, SA 141, SA 261, SA 41). The remaining sample set of 17 severe asthmatics (SA), 19 mild asthmatics (MA) and 18 controls (ctrl) were used for down-stream analysis.
2011-12-01 | E-GEOD-27011 | 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