Prevention and treatment of food allergy by specific glycation and peptide-based oral immunotherapy

食物过敏的患病率因国家而异，在北美，儿童为4-8%，成人为1-5%。最早的过敏病例（6个月前发病）主要涉及牛奶，然后是鸡蛋（第二常见的食物过敏原）。目前还没有治疗食物过敏的方法。然而，在儿童中，耐受性可以自然实现，一些过敏可能会随着年龄的增长而减少或消失。三分之二的鸡蛋过敏儿童在5岁时获得耐受性，然而，35%的儿童终生过敏。在之前的工作中，我们通过位点定向诱变和糖基化证明了基因工程卵细胞样蛋白（OVM）（一种主要的鸡蛋过敏原）可以调节鸡蛋过敏小鼠模型的过敏反应并诱导耐受性。此外，我们报道了口服合成卵清蛋白（OVA）多t细胞表位可以通过激发FoxP3和tgf - β相关机制抑制鸡蛋过敏小鼠的过敏反应。这些糖基化和基于肽的免疫疗法代表了一种有吸引力的方法来靶向干预食物过敏。在这种观点下，我们进一步研究了利用不同类型的糖基化形式的OVA（葡萄糖、d -甘露糖、葡甘露聚糖和半乳甘露聚糖）和源自OVM的热变性蛋清蛋白的肽对鸡蛋过敏粘膜耐受的系统性诱导。树突状细胞的抗原摄取和递呈的离体研究将进行。建立的鸡蛋过敏Balb/c模型将用于体内研究。胃肠道（GI）粘膜免疫反应将通过分析血清组胺、特异性IgE、IgG、各种细胞因子分泌、胃肠道局部基因表达和CD4细胞分析等生物标志物来表征。其中，Th1、Th2、Th17和T reg细胞及其toll样受体功能是本研究的主要目标。我们将研究口服耐受诱导的机制，并探索治疗和预防食物过敏的新的免疫治疗策略。

The prevalence of food allergies varies across countries and it ranges 4-8% in children and 1-5% in adults in North America. Earliest allergy cases (onset before the age of 6 months) involve mainly cow's milk and then allergies to egg (2nd most common food allergen). There is currently no treatment for food allergy. However, in children, tolerance can be naturally achieved and some allergies may diminish or disappear with age. The two-third of egg allergy children acquire tolerance at the age of 5 years, however, 35% of children remain allergic throughout their lives. In the previous work, we demonstrated genetically engineered ovomucoid (OVM) (one of major egg allergens) by means of site-directed mutagenesis and glycosylation can modulate allergic responses and induce tolerance in egg allergy mouse model. Furthermore, we reported that orally administered synthetic ovalbumin (OVA) multiple T-cell epitopes can suppress allergic responses in an egg allergy mouse by the elicitation of FoxP3 and TGF-beta associated mechanisms. These glycation and peptide-based immunotherapy represents an attractive approach for targeting interventions in food allergy. In this view, we further study systematic induction of mucosal tolerance of egg allergy using various types of glycation forms of OVA (glucose, D-mannose, glucomannan, , and galactomannan) and peptides derived from OVM depleted heat denatured egg white proteins. Ex-vivo study on antigen uptake and presentation by dendritic cells will be performed. An established egg allergy Balb/c model will be used in vivo study. Gastrointestinal (GI) mucosal immune responses will be characterized by analyzing various biomarkers of serum histamine, specific IgE, IgG, various cytokine secretion, GI local gene expression and CD4 cell analysis. Particularly, Th1, Th2, Th17 and T reg cells and toll like receptor functions are main target in this study. We will examine the mechanism of oral tolerance induction and explore novel immunotherapeutic strategies for treatment and prevention of food allergy.