Delayed anaphylaxis to beef and pork: mechanisms and causes of a new food allergy

对牛肉和猪肉的迟发性过敏反应：新食物过敏的机制和原因

基本信息

批准号：
8053374
负责人：
Scott Palmer Commins
金额：
$ 19.06万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8053374
关键词：
Adult Allergens Allergic Allergic Reaction Amblyomma Anaphylaxis Angioneurotic Edema Animal Model Antibodies Antibody Formation Antigens Area Awareness Basophils Binding Biological Assay Bite Blood Circulation Blood typing procedure Breathing Canis familiaris Carbohydrates Cells Cetuximab Chiggers Chylomicrons Clinical Dermacentor Development Diagnosis Double-Blind Method Eating Educational process of instructing Epidemiology Etiology Event Food Hypersensitivity Helminths Histamine Release Hour Hypersensitivity IgE In Vitro Individual Infection Investigation Life Lipids Mammals Measures Meat Medical Monoclonal Antibodies Mus Oligosaccharides Oral Patients Physicians Population Production Pruritus Reaction Recording of previous events Reporting Research Risk Management Role Route Screening procedure Seeds Serological Severities Shock Symptoms Testing Thoracic Duct Ticks Time United States Urticaria Welts Work base beef blood group cohort design disorder risk food allergen food challenge galactosyl-(1-3)galactose in vivo insight mast cell novel programs research study response sugar

项目摘要

DESCRIPTION (provided by applicant): Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal. In instances where the triggering allergen is not known, establishing the cause of anaphylaxis is pivotal to long-term risk management. Determining the etiology is limited, however, to known causes of anaphylaxis. Therefore, identification of novel causative agents will provide an important step forward by reducing risk of disease and facilitating new, specific treatment approaches. The overarching hypothesis for this proposal is that IgE antibodies to carbohydrates are a major factor in anaphylaxis that currently appears to be idiopathic. We have recently identified and described a carbohydrate, alpha-gal, as a novel food allergen. Patients who have IgE antibodies to alpha-gal report delayed anaphylaxis or urticaria occurring 3-6 hours after eating beef, pork or lamb. By understanding the factors that control this reaction and contribute to the delay, the proposed research will provide insight into the factors that control anaphylaxis and advance the field of food allergy. A delay of 3-6 hours is most unusual in patients with classical food allergy and warrants investigation of the mechanism(s) involved. Using ex-vivo histamine release and basophil activation studies, we will determine whether IgE to alpha-gal can produce activation of these cells. Most patients who have IgE to alpha-gal tolerated mammalian meat for many years. Interestingly, greater than 90% of patients in our cohort who have IgE to alpha-gal report being bitten by large numbers of adult or larval ticks ('seed ticks') in the weeks or months prior to developing symptoms. Hence, these bites may serve as the inciting event in the development of IgE antibodies to alpha-gal and potentially other carbohydrates. Our current work has shown that IgE to the carbohydrate alpha-gal is present in a cohort of patients who report delayed anaphylaxis and allergic reactions after eating mammalian meat. We believe that IgE to alpha-gal and other carbohydrates represents a novel cause of food allergy. The specific aims outlined in this proposal are designed to more accurately define the clinical histories associated with IgE to alpha-gal, elucidate the functional role of this IgE in food allergy and investigate the cause of the delay in symptoms (Specific Aim 1). Specific Aim 2 focuses on the role of ticks in initiating the production of IgE to alpha-gal through establishing the epidemiology of the IgE antibody response to alpha-gal, developing assays for IgE antibodies to tick antigens other than alpha-gal and using animal models to study the IgE antibody response to ticks. Anaphylaxis, or shock, is a severe allergic reaction that can progress quickly and may be fatal if appropriate medical action is not taken. We have identified a group of patients in the Southeastern U.S. who, after being bitten by ticks or chiggers, develop delayed anaphylaxis 3-6 hours after eating beef, pork or lamb and appear to be allergic to a sugar on red meat. Because of the delay, their symptoms would normally be regarded as 'spontaneous' or 'of unknown cause' but understanding why the delay occurs and why adult patients in the Southeast are suddenly becoming allergic to red meat may provide real insight into the factors that control anaphylaxis and food allergy.

描述（由申请人提供）：过敏反应是一种严重的过敏反应，可能会迅速进展并致命。在触发过敏原未知的情况下，确定过敏反应的原因对于长期风险管理至关重要。然而，确定病因仅限于过敏反应的已知原因。因此，识别新的病原体将通过降低疾病风险和促进新的特异性治疗方法向前迈出重要一步。该提议的总体假设是，针对碳水化合物的 IgE 抗体是过敏反应的主要因素，目前这种过敏反应似乎是特发性的。我们最近发现并描述了一种碳水化合物，α-半乳糖，作为一种新型食物过敏原。具有 α-gal IgE 抗体的患者报告称，在食用牛肉、猪肉或羊肉后 3-6 小时会出现迟发性过敏反应或荨麻疹。通过了解控制这种反应并导致延迟的因素，拟议的研究将深入了解控制过敏反应和推进食物过敏领域的因素。对于典型食物过敏患者来说，延迟 3-6 小时是最不常见的，需要研究相关机制。通过离体组胺释放和嗜碱性粒细胞激活研究，我们将确定 IgE 至 α-gal 是否可以激活这些细胞。大多数携带α-gal IgE 的患者多年来都能耐受哺乳动物肉。有趣的是，我们队列中超过 90% 具有 α-gal IgE 的患者报告在出现症状前几周或几个月内被大量成虫或幼虫蜱（“种子蜱”）叮咬。因此，这些叮咬可能会引发针对 α-gal 和其他潜在碳水化合物的 IgE 抗体的产生。我们目前的工作表明，一组报告在食用哺乳动物肉后出现迟发性过敏反应和过敏反应的患者中存在针对碳水化合物 α-gal 的 IgE。我们相信，α-半乳糖和其他碳水化合物的 IgE 代表了食物过敏的新原因。该提案中概述的具体目标旨在更准确地定义与 IgE 至 α-gal 相关的临床病史，阐明该 IgE 在食物过敏中的功能作用并调查症状延迟的原因（具体目标 1）。具体目标 2 通过建立 IgE 抗体对 α-gal 反应的流行病学、开发 IgE 抗体对 α-gal 以外蜱抗原的检测方法以及使用动物模型，重点关注蜱在启动 IgE 生成 α-gal 中的作用研究 IgE 抗体对蜱虫的反应。过敏反应或休克是一种严重的过敏反应，进展迅速，如果不采取适当的医疗措施，可能会致命。我们在美国东南部发现了一组患者，在被蜱虫或恙螨叮咬后，在食用牛肉、猪肉或羊肉后 3-6 小时出现迟发性过敏反应，并且似乎对红肉中的糖过敏。由于延迟，他们的症状通常被认为是“自发的”或“原因不明”，但了解延迟发生的原因以及为什么东南部的成年患者突然对红肉过敏可能有助于真正了解控制因素过敏反应和食物过敏。