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最常见的原因，大约有1.8%的美国人对牛奶过敏