Methods: Genome wide DNA methylation profiling of CD4+ cells from children with diagnosed food allergy (n=30) and non-allergic children (n=30) was undertaken at birth (neonatal cells) and 12 months (during onset). A comparative analysis of DNA methylation profiles was performed and this data was correlated with gene expression data and functional T-cell assays.
Results: We report the first lines of evidence for epigenetic disruption in association with food allergy. 85 loci were differentially methylated between allergics and non-allergics after adjusting for age (Adj P-Value<0.05 Beta fold change >0.10), and genetic effects. This represented a change in the promoter methylation status in 25 unique genes involved in cellular response to stress, fatty acid beta-oxidation pathways, calcium-activated potassium channel activity, small molecule and vitamin metabolism. Approximately 40% of methylation changes occurred outside known gene-associated regions with unknown significance. An examination of the effects of SNPs on methylation profiles revealed HLA-DQB1 as differentially methylated between allergics and non-allergics, resulting in a quantitative change in gene expression.
Conclusions: DNA methylation profiling of CD4+ cells reveals disruption of several epigenetic pathways that appear to be programmed into the T-cell compartment. Although a proxy marker, the methylation array has genotyping utility and suggests a novel role for SNPs in HLA-DQB1 in association with changes in methylation and gene expression.