Sublingual Immunotherapy for Peanut Allergy

花生过敏的舌下免疫疗法

• 批准号: 7807204
• 负责人: A. Wesley Burks
• 金额: $ 38.27万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7807204
• 关键词: Adult; Age; Allergens; Allergic; Allergic Reaction; Allergy to peanuts; American; Antibodies; Antigens; Appearance; Basophils; Blinded; CD4 Positive T Lymphocytes; Cell membrane; Child; Clinical; Clinical Trials; Control Groups; Cytoplasmic Granules; Data; Development; Diagnosis; Dose; Down-Regulation; Enrollment; Epitopes; Equilibrium; Exposure to; Food; Food Hypersensitivity; Foundations; Funding; Future; Goals; Hypersensitivity; IL2RA gene; IgE; IgG4; Immediate hypersensitivity; Immune Tolerance; Immune response; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Immunologics; Immunology; Immunotherapeutic agent; Immunotherapy; Incidence; Infant; Ingestion; Institutes; Interleukin-10; Intervention; Life; Measures; Mediator of activation protein; Membrane; Molecular Mechanisms of Action; Natural History; Oral; Pathology; Patients; Pattern; Peanuts - dietary; Peripheral; Phenotype; Population; Preventive; Protocols documentation; Public Health; Randomized; Reaction; Regulatory T-Lymphocyte; Reporting; Research Personnel; Resolution; Resources; Risk; Salivary; Secretory Immunoglobulin A; Serum; Symptoms; T cell response; T-Lymphocyte; Testing; Time; United States; Work; base; cohort; cytokine; desensitization; design; egg; food allergen; insight; mast cell; novel; oral tolerance; prospective; public health relevance; response; sublingual immunotherapy

DESCRIPTION (provided by applicant): Oral tolerance to foods normally develops during the first few years of life. An aberration of oral tolerance, food allergy, occurs in 6% of children and 3.5% of adults in the United States. Peanut allergy is one of the most common of the food allergies occurring in 1% of young children. Interestingly, approximately only 20% of young children with peanut allergy will develop oral tolerance to peanuts by age five. We propose to utilize a form of treatment, sublingual immunotherapy (SLIT) to investigate and possibly hasten the development of oral tolerance to peanuts. This application is based on data from our work and others that allergen-specific SLIT will desensitize and possibly tolerize peanut-allergic subjects. There have not been well-designed previous studies of SLIT for food allergy that have been scientifically rigorous. Our hypothesis is that instituting peanut allergen SLIT early after development of food allergy will clinically desensitize patients by altering basophil/mast cell reactivity and will cause clinical tolerance to develop because of the activity of allergen- specific T regulatory cells. This proposal is based on our preliminary studies that have examined the effects of SLIT in older children with peanut allergy and of oral immunotherapy in peanut- and egg-allergic children. Our approach will be to enroll two cohorts of subjects who have peanut sensitivity (peanut specific IgE > 7 KU/L and significant initial symptoms); one group soon after their development (ages 1 to 5 years) and the second group who have not outgrown their peanut allergy (ages 6 to 11 years) and treat them with peanut SLIT in a prospective randomized, blinded SLIT protocol. We will study the basophil/mast cell reactivity, antigen-specific T cell responses and mucosal and systemic humoral immune responses in these subjects. We are combining the expertise of scientific investigators from the fields of allergy, immunology and pathology and the resources of our NIH-funded GCRC for our studies. Our specific aims are: (1) Determine if allergen-specific SLIT will cause clinical desensitization and tolerance to develop in peanut allergic young children, (2) Determine if the development of the desensitized state to peanut is associated with the down-regulation of mast cells and basophils, (3) Determine if the development of clinical tolerance to peanuts is associated with an increase in the T regulatory phenotype of antigen-activated peripheral CD4+ T cells and (4) Determine the effect of peanut-specific mucosal and systemic humoral immune responses in SLIT on desensitization and oral tolerance. Completion of the studies will provide new information regarding the cellular and molecular mechanisms of action of oral tolerance and allergen-specific SLIT and provide the foundation for the development of novel treatments for food allergy. PUBLIC HEALTH RELEVANCE - PROJECT NARRATIVE: The project is designed to develop a treatment for food allergy. Food allergy effect 6% - 8% of young children and 4% of adults and there are no current preventive treatment available. The development of a treatment and understanding the mechanism of how it works is important for the future treatment of patients with food allergy.

描述（由申请人提供）：对食物的口服耐受性通常在生命的头几年发展。在美国，有6％的儿童和3.5％的成年人发生口服耐受性，食物过敏。花生过敏是1％的幼儿中最常见的食物过敏之一。有趣的是，大约只有20％的花生过敏的幼儿会在五岁时对花生产生口服耐受性。我们建议利用一种治疗形式，舌下免疫疗法（SLIT）来调查并可能加快对花生的口服耐受性的发展。该应用程序基于我们工作的数据，以及其他特定特定的缝隙会脱敏并可能耐受花生过敏的受试者。先前对食物过敏的缝隙研究尚未精心设计，这些研究在科学上是严格的。我们的假设是，食物过敏后早期提早建立花生过敏原裂缝，将通过改变嗜碱性粒细胞/肥大细胞反应性来使患者脱敏患者，并且由于过敏原调控细胞的活性而导致临床耐受性。该提议基于我们的初步研究，该研究检查了裂隙在花生和卵子过敏儿童中花生过敏和口服免疫疗法的老年儿童的影响。我们的方法是招募两个具有花生敏感性的受试者（花生特异性IgE> 7 ku/L和明显的初始症状）；他们的发展后不久（1至5岁）和第二组尚未超过花生过敏（6至11岁），并在预期的随机，盲人缝隙方案中用花生缝处理。我们将研究这些受试者的嗜碱性粒细胞/肥大细胞反应性，抗原特异性T细胞反应以及粘膜和全身体液免疫反应。 我们正在结合过过敏，免疫学和病理学领域的科学研究人员的专业知识，以及我们NIH资助的GCRC的资源进行研究。我们的具体目的是：（1）确定在花生过敏幼儿中会导致过敏原特异性裂隙会导致临床脱敏和耐受力，（（2）确定脱敏状态到花生的发展是否与肥大细胞和basophils的下调有关抗原激活的周围CD4+ T细胞和（4）确定花生特异性粘膜和全身体液免疫反应在裂隙中对脱敏和口服耐受性的影响。研究的完成将提供有关口服耐受性和过敏原特异性缝隙作用的细胞和分子机制的新信息，并为开发食物过敏的新疗法提供基础。 公共卫生相关性 - 项目叙述：该项目旨在为食物过敏开发一种治疗方法。食物过敏作用6％-8％的幼儿和4％的成年人，目前尚无预防治疗。治疗的发展和理解其工作原理的机制对于未来对食物过敏患者的治疗至关重要。