Delayed Anaphylaxis to Mammalian Meat caused by IgE Ab to alpha-gal

α-gal 的 IgE 抗体引起的哺乳动物肉类迟发性过敏反应

• 批准号: 8882578
• 负责人: Scott Palmer Commins
• 金额: $ 29万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-18 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8882578
• 关键词: Abdomen; Accident and Emergency department; Adult; Allergens; Allergic; Allergic Reaction; Amblyomma; Anaphylaxis; Antibodies; Antibody Formation; Antigens; Basophils; Biological Assay; Bite; Blood Circulation; Blood typing procedure; Carbohydrates; Cetuximab; Chest; Collaborations; Consumption; Data; Development; Disease Vectors; Eating; Enrollment; Epidemiology; Epitopes; Etiology; Exposure to; Food; Food Hypersensitivity; Galactose; Glycolipids; Health; Hemolymph; Histology; Hour; Hypersensitivity; IgE; Ingestion; Intravenous; Investigation; Life; MHC Class II Genes; Meat; Mediating; Mediator of activation protein; Medical; Modeling; Mus; Nature; Oklahoma; Oligosaccharides; Patients; Plasma; Polysaccharides; Positioning Attribute; Production; Reaction; Reaction Time; Reporting; Research; Risk Management; Role; Salivary; Salivary Glands; Salivary Proteins; Sampling; Seeds; Serum; Shock; Site; Source; Symptoms; T-Lymphocyte; Testing; Tick-Borne Diseases; Ticks; Time Study; Up-Regulation; Urticaria; Work; allergic response; base; beef; case history; cohort; design; food antigen; galactosyl-(1-3)galactose; in vivo; insight; novel; particle; research study; response

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 etiology of anaphylaxis is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody (Ab) response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), that has been associated with two distinct forms of anaphylaxis: i) immediate onset anaphylaxis during first exposure to intravenous cetuximab, and ii) delayed onset anaphylaxis 3-6 hours after ingestion of mammalian food products (e.g., beef and pork). The overarching hypothesis for this proposal is that defining both the cause and the mechanism of the IgE Ab response to alpha-gal as well as identifying the antigen responsible for the delayed food reactions will provide insight into the factors that govern allergic responses and control anaphylaxis. The significance of investigating these reactions comes not only from the obvious importance of understanding a novel life threatening form of food allergy, but also because of the possibility of defining a totally new mechanism for reactions related to an important food substance. Our plan of research focuses on the epidemiology of IgE Ab to alpha-gal, the antigen that appears in the bloodstream 3-5 hours after eating beef, pork or lamb, and the role of tick bites in initiating the IgE response. 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 represents a novel cause of food allergy. The specific aims outlined in this proposal are designed to investigate the epidemiology of this carbohydrate-directed IgE (Specific Aim #1), elucidate the mechanism for delayed reactions (Specific Aim #1), establish the cause of the IgE response (Specific Aim #2), and investigate the mechanism of specific IgE production against a glycan (Specific Aim #2). Overall, these studies are uniquely positioned to provide insight into a recently recognized allergic response as well as identify the molecules present during an allergic reaction and possibly establish a model for ecto-parasitic tick bites initiating an IgE response.

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，确定过敏反应的病因是长期风险管理的关键。我们最近的工作已经鉴定了对哺乳动物寡糖表位半乳糖-α-1，3-半乳糖（α-gal）的新型IgE抗体（Ab）应答，其与两种不同形式的过敏反应相关：i）首次暴露于静脉内西妥昔单抗期间的速发型过敏反应，和ii）摄入哺乳动物食品（例如，牛肉和猪肉）。该建议的总体假设是，定义IgE Ab对α-gal反应的原因和机制以及确定导致延迟食物反应的抗原将提供对控制过敏反应和控制过敏反应的因素的了解。研究这些反应的意义不仅在于了解一种新的威胁生命的食物过敏形式的明显重要性，而且还因为有可能为与重要食物物质相关的反应定义一种全新的机制。我们的研究计划侧重于IgE抗体对α-半乳糖的流行病学，这种抗原在吃牛肉，猪肉或羊肉后3-5小时出现在血液中，以及蜱叮咬在启动IgE反应中的作用。 我们目前的工作表明，在一组报告食用哺乳动物肉后出现迟发过敏反应和过敏反应的患者中存在对碳水化合物α-半乳糖的IgE。我们认为，α-gal的IgE代表了食物过敏的一种新原因。本提案中概述的特定目的旨在研究这种碳水化合物导向IgE的流行病学（特定目的#1），阐明延迟反应的机制（特定目的#1），确定IgE反应的原因（特定目的#2），并研究针对聚糖的特异性IgE产生的机制（特定目的#2）。总体而言，这些研究具有独特的优势，可以深入了解最近认识到的过敏反应，并确定过敏反应期间存在的分子，并可能建立引发IgE反应的体外寄生蜱叮咬模型。