AN OBSERVATIONAL STUDY OF FOOD ALLERGY

食物过敏的观察性研究

• 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
• 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

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 对食物过敏的发展过程中所涉及的机制只有有限的了解。 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，成功的战略很可能需要针对那些面临可识别风险的人（例如，具有与花生过敏的发展相关的生物标志物的人）。 这项NIH（NIAID）申办的多中心（5个研究中心）观察性研究将在一组有花生过敏风险的牛奶或鸡蛋过敏儿童中研究花生、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。 入组的婴儿将在4.5年的时间内进行评估，在此期间，我们预测约20%的婴儿将出现临床花生过敏，25-50%的婴儿将出现鸡蛋或牛奶过敏。 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。 这一策略应使我们能够描绘，比较和对比生物标志物和免疫学变化与花生过敏的发展和鸡蛋和牛奶过敏的损失，同时评估重要的临床和环境的影响可能占这些过敏症最近令人震惊的上升。 待检验的假设包括： 临床花生过敏的发生与持续（蛋/奶过敏的不消退）与以下相关：过敏原特异性的、Th 2偏斜的T细胞表型的发展;抗原活化的外周CD 4 + T细胞的T调节表型的减少;与没有临床过敏的人不同的表位特异性IgE抗体谱的发展; Toll样受体（TLR）多态性和损害TLR配体反应性的相关基因;早期暴露于过敏蛋白（通过母乳或口服接触）或同源蛋白质（大豆）;不严格避免致病蛋白质;低暴露于环境中的TLR配体（灰尘内毒素，宠物所有权，兄弟姐妹的数量，日托，抗生素使用等）;和特应性皮炎的严重程度。