PMID- 25859290 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150410 LR - 20181113 IS - 1868-7075 (Print) IS - 1868-7083 (Electronic) IS - 1868-7075 (Linking) VI - 7 IP - 1 DP - 2015 TI - 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. PG - 38 LID - 10.1186/s13148-015-0070-8 [doi] LID - 38 AB - 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-gamma)-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-gamma 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-gamma 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. FAU - Berni Canani, Roberto AU - Berni Canani R AD - 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. FAU - Paparo, Lorella AU - Paparo L AD - Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy. FAU - Nocerino, Rita AU - Nocerino R AD - 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. FAU - Cosenza, Linda AU - Cosenza L AD - Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy. FAU - Pezzella, Vincenza AU - Pezzella V AD - Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy. FAU - Di Costanzo, Margherita AU - Di Costanzo M AD - Department of Translational Medical Science, University of Naples 'Federico II', Via S.Pansini, 5 80131 Naples, Italy. FAU - Capasso, Mario AU - Capasso M AD - 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. FAU - Del Monaco, Valentina AU - Del Monaco V AD - 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. FAU - D'Argenio, Valeria AU - D'Argenio V AD - 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. FAU - Greco, Luigi AU - Greco L AD - 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. FAU - Salvatore, Francesco AU - Salvatore F AD - 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. LA - eng PT - Journal Article DEP - 20150331 PL - Germany TA - Clin Epigenetics JT - Clinical epigenetics JID - 101516977 PMC - PMC4391731 OTO - NOTNLM OT - Epigenetics OT - Extensively hydrolyzed casein formula OT - Food allergy OT - Hypoallergenic formulae OT - Interferon-gamma OT - Interleukin-10 OT - Interleukin-4 OT - Interleukin-5 OT - Lactobacillus rhamnosus GG EDAT- 2015/04/11 06:00 MHDA- 2015/04/11 06:01 PMCR- 2015/03/31 CRDT- 2015/04/11 06:00 PHST- 2014/12/22 00:00 [received] PHST- 2015/03/10 00:00 [accepted] PHST- 2015/04/11 06:00 [entrez] PHST- 2015/04/11 06:00 [pubmed] PHST- 2015/04/11 06:01 [medline] PHST- 2015/03/31 00:00 [pmc-release] AID - 70 [pii] AID - 10.1186/s13148-015-0070-8 [doi] PST - epublish SO - Clin Epigenetics. 2015 Mar 31;7(1):38. doi: 10.1186/s13148-015-0070-8. eCollection 2015.