Journal article
DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease
American journal of respiratory cell and molecular biology, Vol.60(1), pp.96-105
01/2019
DOI: 10.1165/rcmb.2018-0177OC
PMCID: PMC6348713
PMID: 30141971
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 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.
Details
- Title: Subtitle
- DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease
- Creators
- Ivana V. Yang - Colorado School of Public HealthIain Konigsberg - University of Colorado DenverKristyn MacPhail - National Jewish HealthLi Li - National Jewish HealthElizabeth J. Davidson - University of Colorado DenverPeggy M. Mroz - National Jewish HealthNabeel Hamzeh - National Jewish HealthMay Gillespie - National Jewish HealthLori J. Silveira - National Jewish HealthTasha E. Fingerlin - University of Colorado DenverLisa A. Maier - Colorado School of Public Health
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.60(1), pp.96-105
- DOI
- 10.1165/rcmb.2018-0177OC
- PMID
- 30141971
- PMCID
- PMC6348713
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Language
- English
- Date published
- 01/2019
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984359570202771
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