Integrated Genomic and Functional Studies of Tolerance Therapy for Peanut Allerg

花生过敏耐受疗法的综合基因组和功能研究

• 批准号: 8699865
• 负责人: Stephen Joseph Galli
• 金额: $ 5.42万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699865
• 关键词: Accident and Emergency department; Adult; Adverse reactions; Allergens; Allergic; Allergic Disease; Allergy to peanuts; Anaphylaxis; B-Lymphocytes; Basophils; Blood; Blood Tests; Cell physiology; Cessation of life; Child; Clinical; Clonal Expansion; DNA Sequence; Data; Data Analyses; Development; Diagnosis; Disease; Dose; Event; Food; Food Hypersensitivity; Functional disorder; Goals; Hospitals; Human; Immune; Immune response; Immune system; Immunologic Monitoring; Immunophenotyping; Individual; Ingestion; Laboratories; Maintenance; Measurement; Measures; Monitor; Nature; Nuts; Patients; Peanuts - dietary; Phase II Clinical Trials; Phenotype; Placebo Control; Placebos; Population; Protocols documentation; Public Health; Randomized; Regimen; Regulatory T-Lymphocyte; Research; Research Personnel; Resources; Risk; Safety; Sampling; Serological; Severities; Sum; Surveys; T-Lymphocyte; Testing; Time; Treatment Protocols; Trees; Work; analytical method; desensitization; effective therapy; experience; food allergen; functional genomics; improved; innovation; member; multidisciplinary; novel strategies; oral immunotherapy; peripheral blood; response; success

Food allergies have become a world-wide public health problem, and allergy to peanuts is particularly problematic. In the U.S., ingestion of offending food allergens is the single most common cause of anaphylaxis seen in hospital emergency departments, and it is estimated that about 30,000 food-induced anaphylactic events are seen in U.S. emergency departments each year; sadly, about 200 of these events prove fatal. Either peanuts or tree nuts cause the majority of these deaths, and a recent survey in the U.S. found that 1.4% of the population is allergic to peanuts or tree nuts. Prior trials of immune desensitization using traditional and rush allergen protocols in patients with peanut allergy (PA) have shown partial rates of response but, unfortunately, have resulted in high rates of adverse reactions, including anaphylaxis. Recently, landmark studies by Dr. A. Wesley Burks and colleagues have shown success in desensitizing peanut-allergic children to peanut via an oral immunotherapy (OIT) protocol. The Stanford Alliance for Food Allergy Research (SAFAR, pronounced "safer") is a multidisciplinary group whose goals are: 1) to develop and exploit state-of-the-art analytical methods, including advances in human immune monitoring, to improve understanding ofthe immune responses that give rise to food allergies and that underlie promising new approaches to treat this disorder, and 2) to contribute to the development and testing of improved approaches to diagnose, monitor, and treat subjects with food allergies. In this U19 application, we propose to conduct a large placebo-controlled, randomized, phase 2 clinical trial of OIT in children and adults with PA and to measure a broad range of cellular, serologic, and clinical findings in longitudinal samples from PA patients undergoing the trial, as well as from appropriate control subjects (namely, groups of placebo-treated PA subjects, healthy controls, and atopic controls without PA). These data will be used to determine how key immune system parameters are altered during OIT, and which are most predictive of the nature and durability of patient responses to this therapy. In addition, we seek to define immune monitoring parameters, including findings derived from analyses of basophil phenotype and function that can be rapidly performed In a clinical laboratory using very small amounts of blood, that could be used to predict the clinical reactivity to peanut in PA subjects, to improve the safety and efficacy of OIT protocols, and/or to tailor the OIT protocol to each individual subject. We hope that such work will help to achieve the goal of devising a safe and effective curative treatment of this severe disorder.

食物过敏已成为世界性的公共卫生问题，其中花生过敏问题尤为严重。在美国，摄入有害的食物过敏原是医院急诊科发生过敏反应的最常见原因，据估计，美国急诊科每年会发生约 30,000 起由食物引起的过敏事件；遗憾的是，其中约 200 起事件被证明是致命的。其中大部分死亡是花生或坚果造成的，美国最近的一项调查发现，1.4% 的人口对花生或坚果过敏。先前对花生过敏（PA）患者使用传统和灯心过敏原方案进行免疫脱敏试验显示出部分反应率，但不幸的是，导致了包括过敏反应在内的高不良反应发生率。最近，A. Wesley Burks 博士及其同事进行的具有里程碑意义的研究表明，通过口服免疫疗法 (OIT) 方案成功地使花生过敏儿童对花生脱敏。 斯坦福食物过敏研究联盟（SAFAR，读作“更安全”）是一个多学科团体，其目标是：1）开发和利用最先进的分析方法，包括人类免疫监测方面的进步，以提高对引起食物过敏的免疫反应的理解，并为治疗这种疾病的新方法提供基础；2）为改进诊断方法的开发和测试做出贡献， 监测和治疗食物过敏的受试者。在此 U19 申请中，我们建议对患有 PA 的儿童和成人进行一项大型安慰剂对照、随机、2 期 OIT 临床试验，并测量接受试验的 PA 患者以及适当对照受试者（即安慰剂治疗的 PA 受试者组、健康对照和无 PA 的特应性对照）的纵向样本的广泛细胞、血清学和临床结果。这些数据将用于确定关键免疫系统参数在 OIT 期间如何改变，以及哪些最能预测患者对该疗法的反应的性质和持久性。此外，我们寻求定义免疫监测参数，包括嗜碱性粒细胞表型和功能分析得出的结果，这些结果可以在临床实验室中使用极少量的血液快速进行，可用于预测 PA 受试者对花生的临床反应性，以提高 OIT 方案的安全性和有效性，和/或为每个受试者量身定制 OIT 方案。我们希望此类工作将有助于实现为这种严重疾病设计安全有效的治疗方法的目标。