AN OBSERVATIONAL STUDY OF FOOD ALLERGY

食物过敏的观察性研究

基本信息

批准号：
7718173
负责人：
SCOTT H SICHERER
金额：
$ 1.14万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7718173
关键词：
Accounting Allergens Allergic Allergy to eggs Allergy to peanuts Antibiotics Antibodies Antigens Atopic Dermatitis Biological Markers CD4 Positive T Lymphocytes Candidate Disease Gene Child Clinical Computer Retrieval of Information on Scientific Projects Database Development Diet Dust Endotoxins Enrollment Environment Environmental Exposure Epitopes Exposure to Food Hypersensitivity Funding Genes Genetic Genetic Polymorphism Grant Homologous Protein Human Milk Hypersensitivity IgE Immune Immunologics Infant Institution Intervention Ligands Milk Milk Hypersensitivity National Institute of Allergy and Infectious Disease Numbers Observational Study Oral Outcome Ownership Peanuts - dietary Peripheral Persons Phenotype Proteins Recruitment Activity Research Research Personnel Resolution Resources Risk Severities Siblings Site Source T-Cell Development T-Lymphocyte Testing Time Toll-like receptors United States National Institutes of Health cohort developmental immunology egg experience prevent soy

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is only a limited understanding of the mechanisms involved in the developmental course of food allergies. To effectively prevent or reverse the progression of food allergy, immune interventions will be needed. Furthermore, it is likely that successful strategies will need to be directed to those persons at identifiable risk (e.g., who have biomarkers associated with development of peanut allergy). This NIH (NIAID) sponsored multi-center (5 sites) observational study will investigate the developmental immunology of peanut, egg and milk allergy in a cohort of milk or egg allergic children who are at risk for peanut allergy. We will recruit 400 infants (approximately 80 at Mount Sinai) with milk or egg allergy and approximately 250 sibling controls (approximately 50 at Mount Sinai) for genetic and immunological studies. Enrolled infants will be evaluated over a 4.5 year period during which time we predict that approximately 20% will develop clinical peanut allergy and 25-50% will experience resolution of egg or milk allergy. We will perform directed immune testing (T cell studies, humoral studies), explore candidate genes that may influence food allergy (toll like receptor polymorphisms) and evaluate environmental exposures and diet that may influence outcomes. This strategy should enable us to delineate, compare and contrast biological markers and immunologic changes associated with the development of peanut allergy and loss of egg and milk allergy while simultaneously evaluating important clinical and environmental influences likely to account for the recent alarming rise in these allergies. Hypotheses to be tested include: The development and persistence of clinical peanut allergy (non-resolution of egg/milk allergy) is associated with: the development of an allergen-specific, Th2- skewed T cell phenotype; a decrease in the T regulatory phenotype of antigen-activated peripheral CD4+ T cells; development of an epitope-specific IgE antibody profile that is distinct from persons without clinical allergy; Toll-like receptor (TLR) Polymorphisms and related genes that impair responsiveness to TLR ligands; Early exposure to allergenic proteins (via breast milk or oral exposure) or homologous proteins (soy); less than strict avoidance of the causal proteins; Low exposure to TLR ligands in the environment (dust endotoxin, pet ownership, number of siblings, daycare, antibiotic use, etc); and the severity of atopic dermatitis.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。对食物过敏发展过程中涉及的机制了解有限。为了有效预防或逆转食物过敏的进展，需要进行免疫干预。此外，成功的策略可能需要针对那些具有可识别风险的人（例如，具有与花生过敏发展相关的生物标志物的人）。这项美国国立卫生研究院 (NIAID) 赞助的多中心（5 个地点）观察性研究将调查一组有花生过敏风险的牛奶或鸡蛋过敏儿童中花生、鸡蛋和牛奶过敏的发育免疫学。我们将招募 400 名患有牛奶或鸡蛋过敏的婴儿（西奈山约 80 名）和约 250 名兄弟姐妹对照（西奈山约 50 名）进行遗传和免疫学研究。登记的婴儿将在 4.5 年的时间内接受评估，在此期间，我们预测大约 20% 的婴儿会出现临床花生过敏，25-50% 的婴儿会经历鸡蛋或牛奶过敏的缓解。我们将进行定向免疫测试（T 细胞研究、体液研究），探索可能影响食物过敏的候选基因（Toll 样受体多态性），并评估可能影响结果的环境暴露和饮食。这一策略应该使我们能够描述、比较和对比与花生过敏的发生以及鸡蛋和牛奶过敏的消失相关的生物标志物和免疫学变化，同时评估可能解释这些过敏最近令人震惊的上升的重要临床和环境影响。需要检验的假设包括：临床花生过敏（鸡蛋/牛奶过敏未解决）的发展和持续与以下因素相关：过敏原特异性、Th2 倾斜的 T 细胞表型的发展；抗原激活的外周 CD4+ T 细胞的 T 调节表型减少；开发与没有临床过敏的人不同的表位特异性 IgE 抗体谱； Toll 样受体 (TLR) 多态性和相关基因会损害 TLR 配体的反应性；早期接触过敏性蛋白质（通过母乳或口腔接触）或同源蛋白质（大豆）；不严格避免致病蛋白质；环境中 TLR 配体的暴露程度较低（灰尘内毒素、养宠物、兄弟姐妹数量、日托、抗生素使用等）；以及特应性皮炎的严重程度。