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

American Journal of Respiratory Cell and Molecular Biology
Ivana V YangLisa A Maier

Abstract

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 immu...Continue Reading

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Citations

Oct 16, 2018·American Journal of Respiratory Cell and Molecular Biology·Samuel Brusca, Sean Agbor-Enoh
Jun 6, 2020·American Journal of Respiratory and Critical Care Medicine·Swati PhalkePhilippa Marrack
Aug 28, 2020·Frontiers in Immunology·Landon W LockeElliott D Crouser
Aug 9, 2020·Scientific Reports·Maneesh BhargavaL A Maier
Jan 2, 2021·Pulmonary Therapy·Kevin P Vlahovich, Akshay Sood
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Jun 28, 2021·Current Opinion in Pulmonary Medicine·Els Beijer, Marcel Veltkamp
Jun 28, 2021·Current Opinion in Pulmonary Medicine·Paolo Spagnolo, Lisa A Maier

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Datasets Mentioned

BETA
GSE110780

Methods Mentioned

BETA
PCR
Methylation Profiling
PCA

Software Mentioned

Pyromark Assay Design Software
IPA
Partek Genomics Suite
NetworkAnalyst
Network Analyst
Ingenuity Pathway Analysis ( IPA )

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