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: 7476105
• 负责人: Hugh A Sampson
• 金额: $ 53.62万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476105
• 关键词: Accident and Emergency department; Adverse effects; Affect; Allergens; Allergic; Allergic Reaction; American; Anaphylaxis; Antibodies; Asthma; Basophils; Biological Markers; Blinded; Caring; Caseins; Cattle; Cell physiology; Cells; Child; Childhood; Clinical; Country; Data; Dendritic Cells; Development; Diagnosis; Diet; Disease; Double-Blind Method; Epitopes; Food; Food Hypersensitivity; Frequencies; Health; Heating; Hypersensitivity; IgE; Immune; Immunoglobulin G; Immunologics; Immunotherapy; Individual; Infant; Ingestion; Lactalbumin; Lead; Life; Mediating; Medical; Methods; Milk; Milk Hypersensitivity; Milk Proteins; Monitor; Nature; Newborn Infant; Nuts; Observational Study; Oral; Patients; Peanuts - dietary; Personal Satisfaction; Phenotype; Placebo Control; Population; Progress Reports; Proteins; Reporting; Role; Seafood; Standards of Weights and Measures; Structure; Subgroup; T-Lymphocyte; Th2 Cells; Therapeutic; Wheat; Whey Protein; base; clinical phenotype; desensitization; egg; insight; man; novel; omalizumab; oral tolerance; research study; respiratory; response; soy; sublingual immunotherapy; 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，约占美国的1.8％ 开发IgE介导的对牛奶的过敏反应[约74,000例]。而-80％的“出口” 他们的牛奶过敏到六岁生日，35％将发展其他食物过敏，约60％发展 呼吸过敏和哮喘。牛奶过敏提供了研究免疫学的理想“自然实验” 与食物和过敏性疾病的口服耐受性相关的机制。这是最常见的 美国儿童的食物过敏，反映出“瞬态”的食物过敏形式，即“超越”， 类似于许多其他儿童食品过敏[例如鸡蛋，大豆，小麦]和“持久”，更严重的形式， 类似于花生，坚果和海鲜过敏。它可以被确定地诊断出患有盲食挑战 负责任的过敏原，牛奶蛋白，包括其3维结构。 尽管严格的避税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，大多数儿童将忍受没有有害影响的热贬低产品。在 此外，口服免疫疗法[OIT]的初步研究报告了Milkallergic的有效“脱敏” 患者，但是通过这种疗法可以诱导真正的“耐受性”，还有待证明。 在该项目的AIM＃1中，我们将根据其牛奶过敏患者的临床表型 对各种形式的热增生牛奶蛋白的反应，识别新型的生物标志物来区分 亚组，并阐明了耐受性获得的免疫学变化。此外，我们 假设在儿童的儿童中，向免疫耐受性的进展将更快地发生 积极摄入牛奶蛋白，这种耐受性将与体液的明显变化有关 细胞功能。在AIM＃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看到的“脱敏”相比，临床“耐受性”，并监测相关的 免疫学变化。与该中心申请中的其他项目一起，成功完成 这些目标将为与口腔发展相关的免疫学变化提供新的见解 对食物的耐受性，表型和免疫学差异，牛奶过敏性差异，可能 导致牛奶过敏患者的医疗管理和治疗方面的新​​范式。