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.

牛奶是儿童食物过敏的最常见原因，大约 1.8% 的美国人对牛奶过敏。 婴儿对牛奶产生 IgE 介导的过敏反应 [约 74,000 例/年]。而-80%“不再增长” 到 6 岁生日时对牛奶过敏，35% 的人会出现其他食物过敏，约 60% 的人会出现过敏 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” 与食物和过敏性疾病的口服耐受诱导相关的机制。这是最常见的 美国儿童的食物过敏反映了食物过敏的“暂时”形式，即“不再适应”， 与许多其他儿童食物过敏相似[例如鸡蛋、大豆、小麦]，以及“持久性”更严重的形式， 类似于花生、坚果和海鲜过敏。通过盲食挑战可以明确诊断 引起过敏的牛奶蛋白，包括其 3 维结构，均得到了很好的表征。 尽管严格避免牛奶饮食一直是牛奶过敏患者的“护理标准”，但我们最近 数据表明，大多数儿童能够耐受热变性产品而不会产生有害影响。在 此外，口服免疫疗法[OIT]的初步研究报告了对牛奶过敏的有效“脱敏” 患者，但这种疗法是否可以诱导真正的“耐受性”仍有待证明。 在该项目的目标#1中，我们将根据牛奶过敏患者的临床表型来描述他们的临床表型。 对各种形式的热变性乳蛋白的反应，识别区分不同形式的新型生物标志物 亚组，并阐明伴随获得耐受性的免疫变化。此外，我们 假设在以下儿童中，免疫耐受的进展会更快 积极摄入乳蛋白，这种耐受性与体液和体液的明显变化有关 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 与单独使用 OIT 所见的“脱敏”相比，临床“耐受性”，并监测相关 免疫学变化。结合本中心其他项目申请，顺利完成 这些目标将为了解与口腔疾病发展相关的免疫学变化提供新的见解。 对食物的耐受性，描绘牛奶过敏个体的表型和免疫学差异，并且可能 导致牛奶过敏个体的医疗管理和治疗的新范例。