Mechanisms underlying the physiological and cellular response to food allergen challenge in human subjects with peanut allergy

花生过敏人类受试者对食物过敏原挑战的生理和细胞反应的机制

• 批准号: MR/K010468/1
• 负责人: Paul Turner
• 金额: $ 158.58万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK010468%2F1
• 关键词: Mechanisms; underlying; physiological; cellular; response

Food allergy affects up to 2% of adults and 8% of children in the UK, and can cause life-threatening reactions (anaphylaxis) in some but not all individuals. The mainstay of management remains dietary avoidance. There is no effective treatment for preventing allergic reactions, which can be fatal even when rescue medication is given in a timely manner.Allergic reactions to food are mediated through the Immunoglobulin E (IgE) antibody. The binding of allergenic proteins in food to IgE causes the release of different chemical mediators, including histamine. Much of our knowledge of the mechanism is derived from animal models, but this may not be representative of the situation in man. Antihistamines can prevent fatality in animal models of anaphylaxis but are much less effective in man, possibly because humans are 1000-fold more sensitive to the effects of histamine than, for example, mice. Furthermore, anaphylaxis in peanut-allergic humans can be triggered by tiny amounts of protein (under 10mg or 1/30 of a single peanut). By comparison, very high levels are required to cause anaphylaxis by the oral route in mouse models, equivalent to a person eating over 1000 peanuts. These examples demonstrate the difficulties of extrapolating data from animal models to man.The diagnosis of food allergy can be confirmed by the detection of specific IgE to the trigger food, either by blood or skin testing. Unfortunately, while levels of specific IgE predict the likelihood of reaction after exposure, they do not predict the severity of reaction. While some risk factors have been identified for anaphylaxis (e.g. asthma, underlying heart disease, previous anaphylaxis), the majority of patients do not have a risk factor. Health professionals are therefore unable to determine who is at risk of anaphylaxis, resulting in widespread prescribing of adrenaline auto-injector pens for emergency rescue treatment. The prescription of these devices has increased over the past decade, from 74,600 devices in England in 2000 to over 230,000 devices in 2010, at a cost of £12.5m. The vast majority of these devices are never used, and their prescription is a significant cost to the health service. Any data facilitating improved risk stratification of allergic individuals would assist health professionals in providing reassurance to patients and parents alike, as well as delivering economic savings.Given the importance of dietary avoidance in the management of food allergies, the Food Standards Agency (FSA) is commissioning a study to determine the amount of peanut which needs to be consumed to trigger a reaction. This threshold varies significantly between individuals, but also within the same person, depending on a number of poorly understood factors including exercise. The aim is to define a safe level of potential food contamination below which peanut-allergic individuals will not react, thus informing the food industry and better protecting the allergic population. The study will recruit 100 peanut-allergic volunteers, each undergoing controlled exposure to peanut or placebo under medical supervision on different occasions.The FSA study provides a unique opportunity to assess the mechanism of food allergic reactions, and determine the extent to which data from animal models are applicable to man. We propose to monitor the effects of food allergic reactions on:- the absorption of food proteins in the mouth, to see if this changes as the reaction progresses- the release of different chemical mediators in blood, saliva and urine.- changes in blood flow, both at the site of reaction and beyond, using non-invasive techniquesOur data will provide valuable insight into the mechanisms underlying food allergic reactions in man, highlighting new targets for future diagnostic tests and therapies. We further plan to develop new strategies to improve risk stratification, in order to improve management of peanut allergic individuals.

在英国，食物过敏影响了高达2%的成年人和8%的儿童，并可能在一些但不是所有的人身上引起危及生命的反应（过敏反应）。治疗的主要方法仍然是避免饮食。没有有效的治疗方法来防止过敏反应，即使及时给予抢救药物，也可能是致命的。食物过敏反应是通过免疫球蛋白E （IgE）抗体介导的。食物中的致敏蛋白与IgE的结合会导致不同化学介质的释放，包括组胺。我们对这种机制的大部分知识都来自动物模型，但这可能并不代表人类的情况。在过敏反应的动物模型中，抗组胺药可以预防死亡，但在人类身上的效果要差得多，这可能是因为人类对组胺的影响比老鼠敏感1000倍。此外，花生过敏的人可以通过少量的蛋白质（低于10毫克或1/30个花生）引发过敏反应。相比之下，在小鼠模型中，通过口服途径引起过敏反应需要非常高的水平，相当于一个人吃1000多颗花生。这些例子说明了将动物模型的数据外推到人类身上的困难。食物过敏的诊断可以通过检测对触发食物的特定IgE来确认，可以通过血液或皮肤测试。不幸的是，虽然特定的IgE水平可以预测暴露后发生反应的可能性，但并不能预测反应的严重程度。虽然已经确定了过敏反应的一些危险因素（例如哮喘、潜在心脏病、既往过敏反应），但大多数患者没有危险因素。因此，卫生专业人员无法确定谁有过敏反应的风险，导致在紧急救援治疗中广泛使用肾上腺素自动注射笔。在过去的十年里，这些设备的处方数量不断增加，从2000年的74600台增加到2010年的23万多台，花费了1250万英镑。这些设备中的绝大多数从未使用过，它们的处方对卫生服务来说是一笔巨大的成本。任何有助于改善过敏个体风险分层的数据都将有助于卫生专业人员为患者和家长提供保证，并节省经济成本。考虑到饮食避免在食物过敏管理中的重要性，英国食品标准局（FSA）正在委托进行一项研究，以确定需要摄入多少花生才能引发过敏反应。这个阈值在个体之间有很大差异，但在同一个人内部也有很大差异，这取决于许多鲜为人知的因素，包括运动。其目的是确定潜在食品污染的安全水平，低于该水平花生过敏个体不会产生反应，从而通知食品工业并更好地保护过敏人群。这项研究将招募100名花生过敏的志愿者，每个人在不同的场合在医疗监督下接受花生或安慰剂的控制。FSA的研究提供了一个独特的机会来评估食物过敏反应的机制，并确定动物模型的数据在多大程度上适用于人类。我们建议监测食物过敏反应对以下方面的影响：-口腔中食物蛋白质的吸收，看看这种情况是否随着反应的进展而改变-血液、唾液和尿液中不同化学介质的释放。我们的数据将为人类食物过敏反应的潜在机制提供有价值的见解，为未来的诊断测试和治疗提供新的靶点。我们进一步计划制定新的策略来改善风险分层，以改善花生过敏个体的管理。

项目成果

Precautionary labelling of foods for allergen content: are we ready for a global framework?

• DOI: 10.1186/1939-4551-7-10
• 发表时间: 2014
• 期刊: The World Allergy Organization journal
• 作者: Allen KJ;Turner PJ;Pawankar R;Taylor S;Sicherer S;Lack G;Rosario N;Ebisawa M;Wong G;Mills ENC;Beyer K;Fiocchi A;Sampson HA
• 通讯作者: Sampson HA

Food anaphylaxis in the United Kingdom: analysis of national data, 1998-2018.

• DOI: 10.1136/bmj.n251
• 发表时间: 2021-02-17
• 期刊: BMJ (Clinical research ed.)
• 作者: Baseggio Conrado A;Ierodiakonou D;Gowland MH;Boyle RJ;Turner PJ
• 通讯作者: Turner PJ

Fatal Food Anaphylaxis: Distinguishing Fact From Fiction

致命的食物过敏反应：区分事实与虚构

• DOI: 10.1016/j.jaip.2021.10.008
• 发表时间: 2022
• 期刊: In Practice
• 影响因子: 0.3
• 作者: Anagnostou A

Myths, facts and controversies in the diagnosis and management of anaphylaxis.

• DOI: 10.1136/archdischild-2018-314867
• 发表时间: 2019-01
• 期刊: Archives of disease in childhood
• 影响因子: 5.2
• 作者: Anagnostou K;Turner PJ
• 通讯作者: Turner PJ

Consensus on DEfinition of Food Allergy SEverity (DEFASE) an integrated mixed methods systematic review.

• DOI: 10.1016/j.waojou.2020.100503
• 发表时间: 2021-03
• 期刊: The World Allergy Organization journal
• 作者: Arasi S;Nurmatov U;Dunn-Galvin A;Daher S;Roberts G;Turner PJ;Shinder SB;Gupta R;Eigenmann P;Nowak-Wegrzyn A;Sánchez Borges MA;Ansotegui IJ;Fernandez-Rivas M;Petrou S;Tanno LK;Vazquez-Ortiz M;Vickery BP;Wong GW;Ebisawa M;Fiocchi A
• 通讯作者: Fiocchi A