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Published on: June 16, 2017
Whole-Genome DNA Methylation Profiling of CD14+ Monocytes Reveals Disease Status and Activity Differences in Crohn's
Andrew Y F Li Yim1,2, Nicolette W Duijvis3,4, Mohammed Ghiboub2,3
1Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Genome Diagnostics Laboratory, Amsterdam Reproduction & Development, 1105 AZ Amsterdam, The Netherlands.
Insights
DNA methylation differences in circulating monocytes correlate with Crohn's disease activity. This study reveals epigenetic changes in inflammatory genes, offering insights into disease mechanisms and potential therapeutic targets.
Area of Science:
- Immunology
- Epigenetics
- Gastroenterology
Background:
- Crohn's disease (CD) is a chronic inflammatory bowel disorder with no cure.
- Monocytes differentiate into pro-inflammatory macrophages during CD inflammation.
- Understanding monocyte epigenetic changes is crucial for CD management.
Purpose of the Study:
- To investigate DNA methylation patterns in circulating monocytes from Crohn's disease patients.
- To correlate DNA methylation profiles with disease activity in CD.
- To identify potential epigenetic biomarkers for CD inflammation.
Main Methods:
- Profiling the DNA methylome of circulating monocytes from an all-female cohort.
- Comparing methylation patterns between CD patients (active and remissive) and healthy volunteers.
- Analyzing differentially methylated genes (DMGs) in relation to inflammatory genes and monocyte subsets.
Main Results:
- Identified 15 differentially methylated genes (DMGs) between CD patients and controls.
- Identified 12 DMGs between active CD and remissive CD patients.
- Differential methylation predominantly occurred in promoter regions of inflammation-associated genes.
Conclusions:
- CD activity is linked to distinct DNA methylation patterns in circulating monocytes.
- Epigenetic alterations in inflammatory genes may play a role in CD pathogenesis.
- These findings highlight potential epigenetic targets for managing Crohn's disease.
Abstract:
Crohn's disease (CD) is a multifactorial incurable chronic disorder. Current medical treatment seeks to induce and maintain a state of remission. During episodes of inflammation, monocytes infiltrate the inflamed mucosa whereupon they differentiate into macrophages with a pro-inflammatory phenotype. Here, we sought to characterize the circulating monocytes by profiling their DNA methylome and relate it to the level of CD activity. We gathered an all-female age-matched cohort of 16 CD patients and 7 non-CD volunteers. CD patients were further subdivided into 8 CD patients with active disease (CD-active) and 8 CD patients in remission (CD-remissive) as determined by the physician global assessment. We identified 15 and 12 differentially methylated genes (DMGs) when comparing CD with non-CD and CD-active with CD-remissive, respectively. Differential methylation was predominantly found in the promoter regions of inflammatory genes. Comparing our observations with gene expression data on classical (CD14++CD16-), non-classical (CD14+CD16++) and intermediate (CD14++CD16+) monocytes indicated that while 7 DMGs were differentially expressed across the 3 subsets, the remaining DMGs could not immediately be associated with differences in known populations. We conclude that CD activity is associated with differences in DNA methylation at the promoter region of inflammation-associated genes.
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