Targeted DNA methylation profiling reveals epigenetic signatures in peanut allergy

Abstract

DNA methylation (DNAm) has been shown to play a role in mediating food allergy, however, the mechanism by which it does so is poorly understood. In this study, we used targeted NextGen bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) vs non-allergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity) as well as DNAm signature combinations with superior diagnostic potential compared to serum peanut specific-IgE for PA vs. NA. Further, we found that following peanut protein stimulation, peripheral blood mononuclear cell (PBMCs) from PA participants showed increased production of cognate cytokines compared to NA participants. The varying responses between PA and NA participants may be associated with the interaction between the modification of DNAm and the interference of environment. Using Euclidean distance analysis, we found that the distances of methylation profile comprising 12 DNAm signatures between PA and NA pairs in monozygotic (MZ) twins were smaller than that in randomly paired genetically unrelated individuals, suggesting that PA related DNAm signatures may be associated with genetic factors.

Epigenetics in Food Allergy and Immunomodulation

“…Furthermore, a high similarity between peanut allergic-and non-allergic patients was observed in monozygotic twins compared to randomly-paired genetically unrelated individuals. This indicates that 12 DNA methylation signature-associated peanut allergy was genetically influenced [47]. Another study described different DNA methylation profiling in Th1 and Th2 cells comparing non-allergic and peanut allergic patients.…”

“…The study suggested that the HLA-DR and -DQ gene region likely poses a significant genetic risk for peanut allergy [46]. Another study revealed that DNA methylation profiling on PBMCs from peanut allergic and non-allergic patients in 96 CpG sites, predicting clinical outcomes [47]. They determined several potential new genes associated with peanut allergy, such as BDNF (neurotrophin) and SERPINE1 (serine protease inhibitor), showing a new research line to elucidate the molecular basis of peanut allergy.…”

The Interplay of Nutriepigenomics, Personalized Nutrition and Clinical Practice in Managing Food Allergy

“…This indicates a better diagnostic biomarker in comparison to serum IgE. However, there are a variety of responses between peanut allergy and no allergy samples that could indicate the interaction of these genes with the environmental factors [69].…”

“…The latest next-generation bisulfite sequencing allows greater coverage of each CpG site at promoter/enhancer regions at genes of interest. This technique has evidently evaluated DNA methylation levels on 70 immune-related genes to address the association between methylation at the CpG sites of these genes to the response of peanut allergen [69]. In peanut allergy, 12 genes were hypermethylated, of which 7 of those were potentially novel to food allergy, 3 genes were associated with Th1/Th2 responses, and 2 genes were associated with innate immunity [69].…”

“…This technique has evidently evaluated DNA methylation levels on 70 immune-related genes to address the association between methylation at the CpG sites of these genes to the response of peanut allergen [69]. In peanut allergy, 12 genes were hypermethylated, of which 7 of those were potentially novel to food allergy, 3 genes were associated with Th1/Th2 responses, and 2 genes were associated with innate immunity [69]. Hypermethylation at CpG sites also occurred at both HLA-DQB1 and HLA-DRB1 genes, which are also involved in food allergy, and such effect can be seen through the presence of a single nucleotide polymorphism [70].…”