Immunological Basis of Egg Allergy

鸡蛋过敏的免疫学基础

• 批准号: 7449739
• 负责人: Anna Halina Nowak-Wegrzyn
• 金额: $ 12.87万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7449739
• 关键词: Address; Allergens; Allergic; Allergic Reaction; Allergy to eggs; Antibodies; Antibody Avidity; Arts; Basophils; Binding; Cell Line; Child; Clinical; Clinical Research; Clinical Trials; Commit; Development; Diet; Diet Monitoring; Disruption; Double-Blind Method; Effector Cell; Egg Proteins; Egg White; Egg Yolk Proteins; Environment; Epitopes; Equipment; Feces; Food; Food Hypersensitivity; Gastrointestinal tract structure; Goals; Growth; Heating; Hypersensitivity; IgE; Immunoglobulin G; Immunology; Infant; Ingestion; Intestinal Mucosa; Intestines; Laboratories; Life; Measures; Mediating; Mentors; Monitor; Oral; Outcome; Ovalbumin; Ovomucin; Patients; Pattern; Pattern Recognition; Pepsin A; Peptides; Permeability; Placebo Control; Proteins; Randomized; Rattus; Reaction; Research Personnel; Research Training; Sampling; Serum; Solid; Specificity; Structure; Symptoms; Techniques; Testing; Thiocyanates; Time; Training; Training Programs; anti-IgE; base; career; cooking; design; dietary restriction; egg; experience; leukemia; novel; oral tolerance; patient oriented research; prevent; skills; success; thiocyanate; uptake

DESCRIPTION (provided by applicant): My immediate goal is to acquire skills necessary for an independent career in patient-oriented research. I need training in design and conduct of patient-oriented research as well in immunology laboratory techniques. My long-term objectives are to stablish myself as an investigator in the field of novel therapies for food allergy. I am confident that at Mount Sinai I am in the nurturing environment committed to my success. I will receive highest-quality mentoring from Dr. Hugh A. Sampson and will have strong support from the Food Allergy Laboratory with access to the state-of-the-art equipment. Clinical Research Training Program to develop solid skills in responsible conduct, design, and analysis of clinical research. Egg allergy is one of the most common food allergies in children. Allergic reactions are more frequently caused by egg white than by egg yolk proteins and ovomucoid is the dominant allergen. Previous studies have demonstrated that children with persistent egg allergy have significantly higher concentrations of IgE-anti-ovomucoid antibodies than those who develop tolerance to egg and those with high IgE-binding activity to pepsin-treated ovomucoid are unlikely to outgrow egg white allergy. We propose to test the following hypotheses: 1. Specific Aim # 1: Test the hypothesis that egg-allergic children who can ingest extensively heated (baked) egg proteins without experiencing allergic symptoms lack IgE antibodies to sequential egg epitopes compared with children that react to extensively heated egg and possess IgE antibodies to sequential egg epitopes. Children with egg allergy will be challenged to baked products containing cooked egg proteins. Challenge outcome will be compared to epitope recognition. Children tolerating egg in baked goods will be randomized to receive egg-free or egg containing diet, and monitored for 48 months. Egg protein- and epitope- specific IgE and IgG antibodies, intestinal permeability, and growth will be monitored. 2. Specific Aim # 2: Test the hypothesis that children with more diverse egg IgE epitope recognition patterns have functional consequences on effector cells resulting in more severe reactions and more persistent egg allergy. IgE and IgG antibody avidity and epitope specificity to the two major egg white allergens (ovomucoid and ovalbumin) will be monitored on a yearly basis by peptide array in 90 patients with IgE-mediated egg allergy over 48 months and will be correlated with clinical reactivity to egg determined by double-blinded placebo controlled egg challenges. Antibody avidity will be assessed with thiocyanate disruption. The effector function of IgE antibodies will be assessed by basophil release test with the use of passively sensitized FceRI-transfected rat basophil leukemia cell line stimulated with native and heat-inactivated egg proteins. 3. Specific Aim# 3: Test the hypothesis that egg-specific IgE antibodies facilitate uptake of egg allergen in the gastrointestinal tract and that the concentration of fecal egg-lgE antibody correlates with intestinal permeability and clinical reactivity to egg in children with egg allergy. We postulate that egg-allergic children have anti-egg IgE antibodies detectable in stool, and that luminal anti-egg IgE antibodies facilitate the uptake of egg allergen, resulting in clinical symptoms and increased intestinal permeability. Stool samples will be obtained prior to and following each oral egg challenge (at multiple time points over 48 months) in children participating in a clinical trial described in Aim # 1. Total and egg-specific IgE, egg-lgE and egg-specific IgG will be determined in each stool sample and correlated with clinical outcome of the oral egg challenge. Intestinal permeability will be tested prior to baseline egg challenges in all children participating in Aim # 1 and following oral egg challenges in a smaller subset of patients. Intestinal permeability will also be measured at 3 and 12 months, and correlated with oral egg challenge outcome, fecal and serum anti-egg IgE and anti-egg IgG antibody levels.

描述（由申请人提供）：我的近期目标是获得在以患者为导向的研究中独立职业所需的技能。我需要在设计和实施以病人为导向的研究以及免疫学实验室技术方面的培训。我的长期目标是成为食物过敏新疗法领域的研究人员。我相信，在西奈山，我处在一个培养我成功的环境中。我将接受休·a·桑普森博士的高质量指导并得到食物过敏实验室的大力支持使用最先进的设备。临床研究培训计划，培养负责任的临床研究行为、设计和分析方面的扎实技能。鸡蛋过敏是儿童最常见的食物过敏之一。蛋清比蛋黄蛋白更容易引起过敏反应，而卵泡样蛋白是主要的过敏原。先前的研究表明，与对鸡蛋产生耐受性的儿童相比，持续鸡蛋过敏的儿童的ige -抗卵黏液抗体浓度明显更高，而那些对胃蛋白酶处理的卵黏液具有高ige结合活性的儿童不太可能克服蛋清过敏。