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
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
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DOI：
10.1186/s13148-015-0070-8
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发表时间：
2015-03-31
影响因子：
5.7
通讯作者：
Salvatore, Francesco
中科院分区：
文献类型：
--
作者：
Canani, Roberto Berni;Paparo, Lorella;Salvatore, Francesco
背景：DNA甲基化的表观遗传变化可调节几种过敏相关基因的表达。我们研究了免疫球蛋白E （IgE）介导的牛奶过敏（CMA）儿童的耐受性获得是否与Th2 （IL-4、IL-5）和Th1 （IL-10、ifn - γ）相关细胞因子基因的特异性DNA甲基化谱有关。结果：在ige介导的CMA活跃儿童（1组）、获得牛奶蛋白耐受儿童（2组）和健康儿童（3组）中，评估了外周血单个核细胞基因促进区域CpGs的DNA甲基化以及血清IL-4、IL-5、IL-10和inf - γ水平。40名儿童（24名男孩，年龄3至18个月）被纳入研究：1组10名，2组20名，对照组10名。DNA甲基化谱清楚地将活动性CMA患者与健康对照分开。我们观察到相反的模式，将活跃的ige介导的CMA与健康对照组和2组儿童进行比较。活性ige介导的CMA患者IL-4和IL-5 DNA甲基化显著降低，IL-10和inf - γ DNA甲基化较高。所有细胞因子的基因启动子DNA甲基化率与各自的血清水平密切相关。配方选择显著影响2组细胞因子DNA甲基化谱。结论：ige介导的CMA患儿耐受获得的特点是Th1和Th2细胞因子基因DNA甲基化模式明显。这些结果提示DNA甲基化可能是CMA预防和治疗的靶点。
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.