Sublingual Immunotherapy for Peanut Allergy

花生过敏的舌下免疫疗法

• 批准号: 7614511
• 负责人: A. Wesley Burks
• 金额: $ 38.66万
• 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/7614511
• 关键词: Adult; Age; Allergens; Allergic; Allergic Reaction; Allergy to peanuts; American; Antibodies; Antigens; Appearance; Basophils; Blinded; CD4 Positive T Lymphocytes; Cell membrane; Cells; 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; Reporting; Research Personnel; Resolution; Resources; Risk; Salivary; Secretory Immunoglobulin A; Serum; Symptoms; 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最初几年内形成。在美国，6% 的儿童和 3.5% 的成人出现口腔耐受性异常，即食物过敏。花生过敏是最常见的食物过敏之一，发生率为 1% 的幼儿。有趣的是，大约只有 20% 的花生过敏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）来研究并可能加速花生口服耐受性的发展。该应用程序基于我们和其他人的工作数据，即过敏原特异性 SLIT 将使花生过敏受试者脱敏并可能耐受。此前还没有经过精心设计、科学严谨的 SLIT 治疗食物过敏研究。我们的假设是，在食物过敏发生后尽早开始花生过敏原 SLIT 将通过改变嗜碱性粒细胞/肥大细胞反应性在临床上使患者脱敏，并且由于过敏原特异性 T 调节细胞的活性而导致临床耐受性的发展。该提案基于我们的初步研究，这些研究检查了 SLIT 对花生过敏的较大儿童的影响以及口服免疫疗法对花生和鸡蛋过敏儿童的影响。我们的方法是招募两组对花生过敏的受试者（花生特异性 IgE > 7 KU/L 且初始症状明显）；一组在发育后不久（1 至 5 岁），另一组尚未摆脱花生过敏（6 至 11 岁），并在前瞻性随机、盲法 SLIT 方案中用花生 SLIT 进行治疗。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。 我们将过敏、免疫学和病理学领域科学研究人员的专业知识与 NIH 资助的 GCRC 的资源结合起来进行我们的研究。我们的具体目标是：(1) 确定过敏原特异性 SLIT 是否会导致花生过敏幼儿出现临床脱敏和耐受性，(2) 确定对花生脱敏状态的发展是否与肥大下调相关细胞和嗜碱性粒细胞，(3) 确定对花生的临床耐受性的发展是否与抗原激活的外周 CD4+ T 细胞的 T 调节表型的增加有关，以及 (4) 确定花生特异性的作用SLIT 中粘膜和全身体液免疫反应对脱敏和口服耐受的影响。研究的完成将提供有关口服耐受和过敏原特异性 SLIT 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奠定基础。 公共卫生相关性 - 项目叙述：该项目旨在开发食物过敏的治疗方法。食物过敏对幼儿有 6% - 8% 的影响，对成人有 4% 的影响，目前尚无可用的预防治疗方法。治疗方法的开发和了解其作用机制对于食物过敏患者的未来治疗非常重要。