BACKGROUND Wheat is known as the most widely consumed food all over the world. Although many types of wheat allergy have been recognized, their treatment still has a long way to go due to the complex pathogenesis. Oral immunotherapy (OIT) is under investigation for the treatment of wheat allergies. Previous studies have demonstrated that OIT using intact wheat allergens can induce tolerance, but is accompanied by a high risk of anaphylactic reactions. OBJECTIVES Our objective was to prepare modified wheat allergens with hypoallergenic and tolerance-inducing properties to reduce adverse effects during immunotherapy. METHODS Wheat gliadin was degraded by hydrolysis with pepsin and trypsin, and then the hydrolysate was deamidated with hydrochloric acid. The IgE-binding capacity and T cell reactivity of the degraded gliadins were evaluated in vitro. Pepsin-digested gliadin (peptic-GLI) was applied in a mouse model to investigate whether it would induce oral tolerance. RESULTS Degradation with pepsin decreased IgE-binding capacity and maintained T cell reactivity. Oral administration of peptic-GLI to mice before sensitization and challenge with gliadin could significantly suppress the production of IgE, IgG1, and type 2 T helper cytokines. Moreover, the development of anaphylactic reactions and allergic responses of the small intestine induced by gliadin challenge were inhibited by oral administration of peptic-GLI. CONCLUSIONS The findings of this study indicate that peptic-GLI with low allergenicity and potential for tolerance induction may become useful in wheat immunotherapy with less adverse effects.

中文翻译：

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胃蛋白酶消化的麦醇溶蛋白保留T细胞反应性在小麦过敏小鼠模型中诱导的口服耐受性。

背景技术小麦被认为是全世界消费最广泛的食物。尽管已经认识到许多类型的小麦过敏，但是由于复杂的发病机理，它们的治疗还有很长的路要走。口服免疫疗法（OIT）正在研究中，以治疗小麦过敏。先前的研究表明，使用完整的小麦变应原进行OIT可以诱导耐受性，但伴有过敏反应的高风险。目的我们的目的是制备具有低变应原性和耐受性的改性小麦变应原，以减少免疫治疗期间的不良反应。方法用胃蛋白酶和胰蛋白酶水解小麦醇溶蛋白，然后将其水解产物用盐酸脱酰胺。在体外评估降解的麦醇溶蛋白的IgE结合能力和T细胞反应性。胃蛋白酶消化的麦醇溶蛋白（p消化GLI）被用于小鼠模型，以研究其是否会诱导口服耐受。结果胃蛋白酶降解可降低IgE结合能力并维持T细胞反应性。在对麦醇溶蛋白致敏和攻击之前，对小鼠口服给予消化性GLI可以显着抑制IgE，IgG1和2型T辅助细胞因子的产生。此外，通过口服给予消化性GLI可抑制由麦醇溶蛋白激发引起的小肠的过敏反应和过敏反应的发展。结论这项研究的结果表明，低变应原性和诱导耐受性的消化道GLI可能在小麦免疫治疗中有用，且不良反应较少。