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

IgE 介导的牛奶过敏中牛奶蛋白的免疫反应

• 批准号: 8034293
• 负责人: Hugh A Sampson
• 金额: $ 60.84万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034293
• 关键词: Allergens; Allergic; Allergic Disease; Allergic Reaction; American; Asthma; Biological Markers; Blinded; Cattle; Cell physiology; Child; Childhood; Clinical; Data; Development; Diagnosis; Diet; Food; Food Hypersensitivity; Heating; Hypersensitivity; IgE; Immunologics; Immunotherapy; Individual; Infant; Lead; Mediating; Medical; Milk; Milk Hypersensitivity; Milk Proteins; Monitor; Nature; Nuts; Oral; Patients; Peanuts - dietary; Reporting; Seafood; Subgroup; Wheat; base; clinical phenotype; desensitization; egg; insight; novel; oral tolerance; research study; respiratory; response; soy; standard of care; three dimensional structure

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.

牛奶是导致儿童食物过敏的最常见原因，约有1.8%的美国人 婴儿出现免疫球蛋白E介导的牛奶过敏反应[每年约74,000例]。而-80%的人已经不再需要了 到他们6岁生日时，35%的人会对其他食物过敏，60%的人会发展成 呼吸道过敏和哮喘。牛奶过敏为免疫学研究提供了理想的“自然实验” 与口服诱导食物耐受和过敏性疾病相关的机制。这是最常见的 食物过敏在美国儿童中的分布，反映了食物过敏的“暂时性”形式，这种形式已经“长大”。 类似于许多儿童时期的食物过敏[如鸡蛋、大豆、小麦]，以及更严重的“持续性”过敏， 类似于花生、坚果和海鲜过敏。它可以被明确诊断为盲目食物挑战 而负责的过敏原，牛奶蛋白，包括它们的三维结构，都有很好的特性。 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”，但我们最近 数据显示，大多数儿童会容忍热变性产品，而不会产生有害影响。在……里面 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”。 但这种疗法是否能诱导出真正的“耐受性”还有待证实。 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进行描述。 对不同形式的热变性乳蛋白的反应，识别区分 亚型，并阐明伴随获得耐受性的免疫学变化。此外，我们 假设免疫耐受进展将在以下儿童中发生得更快 主动摄取牛奶蛋白，这种耐受性将与体液和 细胞功能。在目标2中，我们将确定抗LGE和牛奶OIT的组合是否会诱导 临床“耐受性”与单独使用OIT和监视器相关的“脱敏”进行比较 免疫学变化。与本中心申请的其他项目一起，成功完成 这些目标将为与口腔发育相关的免疫学变化提供新的见解 对食物的耐受性，描述牛奶过敏个体的表型和免疫学差异，并可能 为牛奶过敏患者的医疗管理和治疗带来了新的范例。