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DNA Methylation Changes in Lung Immune Cells are Associated with Granulomatous Lung Disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE110780 | GEO | 2018/12/05

REPOSITORIES: GEO

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DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease.

Project description:Epigenetic marks are likely to explain variability of response to antigen in granulomatous lung disease. The objective of this study was to identify DNA methylation and gene expression changes associated with chronic beryllium disease (CBD) and sarcoidosis in lung cells obtained by BAL. BAL cells from CBD (n = 8), beryllium-sensitized (n = 8), sarcoidosis (n = 8), and additional progressive sarcoidosis (n = 9) and remitting (n = 15) sarcoidosis were profiled on the Illumina 450k methylation and Affymetrix/Agilent gene expression microarrays. Statistical analyses were performed to identify DNA methylation and gene expression changes associated with CBD, sarcoidosis, and disease progression in sarcoidosis. DNA methylation array findings were validated by pyrosequencing. We identified 52,860 significant (P < 0.005 and q < 0.05) CpGs associated with CBD; 2,726 CpGs near 1,944 unique genes have greater than 25% methylation change. A total of 69% of differentially methylated genes are significantly (q < 0.05) differentially expressed in CBD, with many canonical inverse relationships of methylation and expression in genes critical to T-helper cell type 1 differentiation, chemokines and their receptors, and other genes involved in immunity. Testing of these CBD-associated CpGs in sarcoidosis reveals that methylation changes only approach significance, but are methylated in the same direction, suggesting similarities between the two diseases with more heterogeneity in sarcoidosis that limits power with the current sample size. Analysis of progressive versus remitting sarcoidosis identified 15,215 CpGs (P < 0.005 and q < 0.05), but only 801 of them have greater than 5% methylation change, demonstrating that DNA methylation marks of disease progression changes are more subtle. Our study highlights the significance of epigenetic marks in lung immune response in granulomatous lung disease.

| S-EPMC6348713 | biostudies-literature

DNA Methylation Changes in Lung Immune Cells are Associated with Granulomatous Lung Disease [CBD Methylation]

Project description:The goal of this study was to investigate and correlate differential methylation and expression in cells from the target organ in non-infectious granulomatous lung diseases, specifically sarcoidosis and chronic beryllium disease (CBD). To that end, cells were collected from patients via bronchoalveolar lavage (BAL), and extracted nucleic acids were hybridized to genome-wide arrays. We conclude that there are many genes that are both differentially methylated and expressed in the BAL fluid of patients with granulomatous lung disease. We identified 2,726 differentially methylated CpGs mapping to 1,944 unique genes when comparing CBD patients to beryllium-sensitized (BeS) individuals without disease. 69% of these genes were also differentially expressed in CBD. Sarcoidosis patients exhibited directional consistency at many loci, but genome-wide significance was not achieved, likely due to heterogeneity in the patient population.

2018-12-05 | GSE110778 | GEO

DNA Methylation Changes in Lung Immune Cells are Associated with Granulomatous Lung Disease [sarcexp]

2018-12-05 | GSE110777 | GEO

DNA Methylation Changes in Lung Immune Cells are Associated with Granulomatous Lung Disease [sarcmeth]

2018-12-05 | GSE110776 | GEO

DNA Methylation Changes in Lung Immune Cells are Associated with Granulomatous Lung Disease [CBD exp]

2018-12-05 | GSE110779 | GEO