Immunologic Responses to Cow's Milk Proteins in IgE-mediated Cow's Milk Allergy

牛奶是儿童食物过敏的最常见原因，约1.8%的美国人 婴儿对牛奶发生IgE介导的过敏反应[~74，000例/年]。而-80%的"成长" 到6岁时，他们的牛奶过敏，35%将发展其他食物过敏，约60%发展 呼吸道过敏和哮喘。牛奶过敏为研究免疫学提供了理想的"自然实验" 与口服食物耐受诱导和过敏性疾病相关的机制。它是最常见的 美国儿童的食物过敏，反映了"暂时"形式的食物过敏， 类似于许多其他儿童食物过敏[例如鸡蛋，大豆，小麦]，以及"持续性"，更严重的形式， 类似于花生、坚果和海鲜过敏。它可以明确诊断与盲食物挑战 而负责的过敏原，乳蛋白，包括它们的三维结构，都得到了很好的表征。 尽管严格的牛奶避免饮食一直是牛奶过敏患者的"护理标准"， 数据表明，大多数儿童将耐受热变性产品而没有有害影响。在 此外，口服免疫疗法[OIT]的初步研究报告了牛奶过敏的有效"脱敏"， 患者，但是否真正的“耐受性”可以诱导这种疗法仍有待证明。 在本项目的目标#1中，我们将根据牛奶过敏患者的临床表型， 对各种形式的热变性乳蛋白的反应，确定区分 亚组，并阐明免疫学的变化，伴随着收购的耐受性。而且我们 假设免疫耐受进展在以下儿童中发生得更快： 积极摄入牛奶蛋白，耐受性将与体液和 细胞功能在目标#2中，我们将确定抗IgE和乳OIT的组合是否将诱导 与单独使用OIT观察到的"脱敏"相比，临床"耐受性"， 免疫变化。结合本中心其他项目申请，顺利完成 这些目的的研究将为研究与口腔癌的发展相关的免疫学变化提供新的视角。 食物耐受性，描述牛奶过敏个体的表型和免疫学差异， 导致医学管理和治疗牛奶过敏个体的新范例。

Cow's milk is the most common cause of food allergy in children, with approximately 1.8% of American infants developing IgE-mediated allergic reactions to cow's milk [~74,000 cases/year]. While -80% "outgrow" their milk allergy by the 6th birthday, 35% will develop other food allergies and about 60% develop respiratory allergy and asthma. Milk allergy provides an ideal "experiment of nature" to study immunologic mechanisms associated with oral tolerance induction to food and allergic disease. It is the most common food allergy in American children and reflects both the "transient" form of food allergy that is "outgrown," similar to many other childhood food allergies [e.g. egg, soy, wheat], and the "persistent," more severe form, similar to peanut, nuts and seafood allergies. It can be definitively diagnosed with the blinded food challenge and the responsible allergens, milk proteins, are well characterized, including their 3-dimensional structures. Although strict milk avoidance diets have been the "standard of care" for milk-allergic patients, our recent data suggest that the majority of children will tolerate heat-denatured products without deleterious effects. In addition, preliminary studies with oral immunotherapy [OIT] have reported effective "desensitization" of milkallergic patients, but whether true "tolerance" can be induced with this therapy remains to be demonstrated. In Aim #1 of this project, we will delineate clinical phenotypes of milk-allergic patients based upon their response to various forms of heat-denatured milk proteins, identify novel biomarkers differentiating the subgroups, and elucidate immunologic changes that accompany acquisition of tolerance. Furthermore, we hypothesize that progression toward immunological tolerance will occur more rapidly in children who are actively ingesting milk protein, and that tolerance will be associated with distinct changes in humoral and cellular function. In Aim #2 we will determine whether the combination of anti-lgE and milk OIT will induce clinical "tolerance" compared to the "desensitization" seen with OIT alone, and monitor associated immunologic changes. In conjunction with the other projects in this Center application, successful completion of these Aims will provide new insight into the immunologic changes associated with the development of oral tolerance to food, delineate phenotypic and immunologic differences in milk-allergic individuals, and possibly lead to a new paradigm in the medical management and treatment of milk-allergic individuals.