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

• 批准号: 7879100
• 负责人: Scott Palmer Commins
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879100
• 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; Food Hypersensitivity; Hand; 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; galactosyl-(1-3)galactose; in vivo; insight; mast cell; novel; programs; research study; response; sugar

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（由申请方提供）：过敏反应是一种严重的过敏反应，可迅速进展并致命。在触发过敏原未知的情况下，确定过敏反应的原因是长期风险管理的关键。然而，确定病因仅限于已知的过敏反应原因。因此，鉴定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。该建议的首要假设是，碳水化合物的IgE抗体是目前似乎是特发性过敏反应的主要因素。我们最近发现并描述了一种碳水化合物，α-半乳糖，作为一种新的食物过敏原。对α-半乳糖有IgE抗体的患者报告在食用牛肉、猪肉或羊肉后3-6小时发生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的因素并推进食物过敏领域。3-6小时的延迟在典型食物过敏患者中是最不寻常的，需要研究所涉及的机制。使用离体组胺释放和嗜碱性粒细胞活化研究，我们将确定是否IgE α-半乳糖可以产生这些细胞的激活。大多数患有α-gal IgE的患者多年来一直耐受哺乳动物肉类。有趣的是，在我们的队列中，超过90%的对α-gal有IgE的患者报告在出现症状之前的几周或几个月内被大量的成年或幼虫蜱（“种子蜱”）叮咬。因此，这些叮咬可能是激发α-半乳糖和其他潜在碳水化合物的IgE抗体产生的事件。 我们目前的工作表明，对碳水化合物α-半乳糖的IgE存在于一组报告吃哺乳动物肉后发生迟发性过敏反应和过敏反应的患者中。我们认为，对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。本提案中概述的具体目标旨在更准确地定义与α-gal IgE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重点关注蜱虫在启动对α-gal的IgE产生中的作用，方法是建立对α-gal的IgE抗体反应的流行病学，开发对除α-gal外的蜱虫抗原的IgE抗体的测定方法，并使用动物模型研究对蜱虫的IgE抗体反应。过敏反应或休克是一种严重的过敏反应，如果不采取适当的医疗措施，可能会迅速进展，并可能致命。我们在美国东南部发现了一组患者，他们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，并且似乎对红肉上的糖过敏。由于延迟，他们的症状通常被认为是“自发的”或“原因不明”，但了解为什么延迟发生，为什么东南部的成年患者突然对红肉过敏，可能会提供真实的洞察控制过敏反应和食物过敏的因素。