Differences in dna methylation profile of th1 and th2 cytokine genes are associated with tolerance acquisition in children with ige-mediated cow’s milk allergy

Roberto Berni Canani, Lorella Paparo, Rita Nocerino, Linda Cosenza, Vincenza Pezzella, Margherita Di Costanzo, Mario Capasso, Valentina Del Monaco, Valeria D’Argenio, Luigi Greco, Francesco Salvatore

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Abstract

Background: Epigenetic changes in DNA methylation could regulate the expression of several allergy-related genes. We investigated whether tolerance acquisition in children with immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) is characterized by a specific DNA methylation profile of Th2 (IL-4, IL-5) and Th1 (IL-10, IFN-γ)-associated cytokine genes. Results: DNA methylation of CpGs in the promoting regions of genes from peripheral blood mononuclear cells and serum level of IL-4, IL-5, IL-10 and INF-γ were assessed in children with active IgE-mediated CMA (group 1), in children who acquired tolerance to cow’s milk proteins (group 2) and in healthy children (group 3). Forty children (24 boys, aged 3 to 18 months) were enrolled: 10 in group 1, 20 in group 2, and 10 in the control group. The DNA methylation profiles clearly separated active CMA patients from healthy controls. We observed an opposite pattern comparing subjects with active IgE-mediated CMA with healthy controls and group 2 children who outgrew CMA. The IL-4 and IL-5 DNA methylation was significantly lower, and IL-10 and INF-γ DNA methylation was higher in active IgE-mediated CMA patients. Gene promoter DNA methylation rates of all cytokines and respective serum levels were strongly correlated. Formula selection significantly influenced cytokine DNA methylation profiles in group 2. Conclusions: Tolerance acquisition in children with IgE-mediated CMA is characterized by a distinct Th1 and Th2 cytokine gene DNA methylation pattern. These results suggest that DNA methylation may be a target for CMA prevention and treatment.

Original languageEnglish
Article numberA001
Pages (from-to)1-9
Number of pages9
JournalClinical Epigenetics
Volume7
Issue number1
DOIs
Publication statusPublished - 2015

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Keywords

  • Epigenetics
  • Extensively hydrolyzed casein formula
  • Food allergy
  • Hypoallergenic formulae
  • Interferon-γ
  • Interleukin-10
  • Interleukin-4
  • Interleukin-5
  • Lactobacillus rhamnosus GG

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Developmental Biology
  • Genetics(clinical)

Cite this

Canani, R. B., Paparo, L., Nocerino, R., Cosenza, L., Pezzella, V., Di Costanzo, M., Capasso, M., Del Monaco, V., D’Argenio, V., Greco, L., & Salvatore, F. (2015). Differences in dna methylation profile of th1 and th2 cytokine genes are associated with tolerance acquisition in children with ige-mediated cow’s milk allergy. Clinical Epigenetics, 7(1), 1-9. [A001]. https://doi.org/10.1186/s13148-015-0070-8