title: 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.
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.
authors: Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy ; European Laboratory for the Investigation of Food-Induced Diseases, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy ; CEINGE-Biotecnologie Avanzate s.c.ar.l, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Roberto
authors: R
authors: Berni Canani
authors: Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Lorella
authors: L
authors: Paparo
authors: Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy ; CEINGE-Biotecnologie Avanzate s.c.ar.l, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Rita
authors: R
authors: Nocerino
authors: Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Linda
authors: L
authors: Cosenza
authors: Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Vincenza
authors: V
authors: Pezzella
authors: Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Margherita
authors: M
authors: Di Costanzo
authors: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico I, Via S.Pansini, 5 80131 Naples, Italy ; CEINGE-Biotecnologie Avanzate s.c.ar.l, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Mario
authors: M
authors: Capasso
authors: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico I, Via S.Pansini, 5 80131 Naples, Italy ; CEINGE-Biotecnologie Avanzate s.c.ar.l, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Valentina
authors: V
authors: Del Monaco
authors: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico I, Via S.Pansini, 5 80131 Naples, Italy ; CEINGE-Biotecnologie Avanzate s.c.ar.l, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Valeria
authors: V
authors: D'Argenio
authors: Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy ; European Laboratory for the Investigation of Food-Induced Diseases, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Luigi
authors: L
authors: Greco
authors: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico I, Via S.Pansini, 5 80131 Naples, Italy ; CEINGE-Biotecnologie Avanzate s.c.ar.l, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy.
authors: Francesco
authors: F
authors: Salvatore
keywords: Epigenetics; Extensively hydrolyzed casein formula; Food allergy; Hypoallergenic formulae; Interferon-γ; Interleukin-10; Interleukin-4; Interleukin-5; Lactobacillus rhamnosus GG