Mepolizumab-induced Changes in Nasal Methylome and Transcriptome to Predict Response in Asthma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1146373 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30186900_1.fastq.gz | Fastqsanger.gz | |||
| SRR30186900_2.fastq.gz | Fastqsanger.gz | |||
| SRR30186901_1.fastq.gz | Fastqsanger.gz | |||
| SRR30186901_2.fastq.gz | Fastqsanger.gz | |||
| SRR30186902_1.fastq.gz | Fastqsanger.gz |
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Project description:We aimed to detect a predictive or early nasal gene expression and/or DNA methylation signature that could identify responders or non-responders to Mepolizumab at one year.
2024-09-02 | GSE274410 | GEO
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:Background Although the type 2 biologics mepolizumab and dupilumab show clinical efficacy in severe asthma, their influence on circulating lymphocytes is largely unknown. Here, we studied their impact on type 2 lymphocytes in severe asthma. Methods We performed high-parameter flow cytometry analysis of peripheral blood mononuclear cells from 40 patients with severe asthma before, and after 4 and 12 months of mepolizumab (n = 33) or dupilumab (n = 7) treatment, focusing on type 2 lymphocytes. Additionally, we performed single-cell RNA sequencing (scRNA-seq) (n = 3) and stimulation experiments of type 2 lymphocytes (n = 3) to explore transcriptional and functional changes associated with mepolizumab treatment. Results Mepolizumab treatment increased circulating type 2 innate lymphoid cell (ILC2), type 2 T helper (Th2) and type 2 cytotoxic (Tc2) cell frequencies, skewing ILC2 towards a CD117low signature with high CD62L expression, and Th2/Tc2 cells towards a CD45RA−CD62L+ central memory phenotype. Dupilumab-treated patients also showed increased frequencies of total ILC2 and CD117low ILC2. Mepolizumab treatment reduced the expression of tissue homing receptors CXCR4 in ILC2, and GPR183 in ILC2, Th2, and Tc2 cells while enhancing their type 2 cytokine producing capability in response to alarmins. Conclusion Mepolizumab increases the frequencies of circulating ILC2, Th2, and Tc2 cells, with reduced tissue homing receptor expression but increased type 2 cytokine production potential. This reveals a potentially new mechanism for how mepolizumab reduces airway inflammation by re-directing trafficking of inflammatory type 2 lymphocytes away from airway-homing, with implications for the possibility of achieving biologics-free remission in asthma.
2025-08-06 | GSE304665 | GEO
Project description:The goal of this investigation was to establish proof of concept that nasal epithelium can be used as a proxy for the airway epithelium in studies of allergic asthma. We collected PBMCs, nasal epithelia, and bronchial epithelia from 12 subjects with allergic asthma and 12 control subjects without asthma, all non-Hispanic white nonsmoker adults. We conclude that genomic profiling of nasal epithelia captures most disease-relevant changes identified in airway epithelia but also provides additional targets that are most likely influenced by exposures. Thus, epigenetic marks in nasal epithelia may prove useful as a biomarker of disease severity and response to treatment or as a biosensor of the environment in asthma.
2017-10-02 | GSE104471 | GEO
Project description:The goal of this investigation was to establish proof of concept that nasal epithelium can be used as a proxy for the airway epithelium in studies of allergic asthma. We collected PBMCs, nasal epithelia, and bronchial epithelia from 12 subjects with allergic asthma and 12 control subjects without asthma, all non-Hispanic white nonsmoker adults. We conclude that genomic profiling of nasal epithelia captures most disease-relevant changes identified in airway epithelia but also provides additional targets that are most likely influenced by exposures. Thus, epigenetic marks in nasal epithelia may prove useful as a biomarker of disease severity and response to treatment or as a biosensor of the environment in asthma.
2017-10-02 | GSE104468 | GEO
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.
2015-11-01 | GSE65163 | GEO
Project description:The Nasal Methylome: A Key to Understanding Allergic Asthma
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Project description:While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined. We aimed to identify multiple distinct molecular mechanisms implicated in asthma exacerbations by characterizing respiratory illnesses among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab versus placebo
2025-08-07 | GSE292059 | GEO
Project description:The Nasal Methylome: A Key to Understanding Allergic Asthma [Agilent]
| PRJNA412792 | ENA
Project description:The Nasal Methylome: A Key to Understanding Allergic Asthma [Illumina]
| PRJNA412793 | ENA