Improved diagnostics in food allergy (ID-in-FA) Study

改进食物过敏诊断 (ID-in-FA) 研究

• 批准号: MR/S036954/1
• 负责人: Paul Turner
• 金额: $ 140.81万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS036954%2F1
• 关键词: Improved; diagnostics; food; allergy; ID

Food allergy is an increasing public health issue, affecting up to 2% of adults and 6% of children in the UK. It is the most common cause of life-threatening allergic reactions (anaphylaxis). An allergic reaction is a consequence of an interaction between allergen-specific Immunoglobulin E (IgE) antibodies and a food allergen, causing activation of immune cells including mast cells found throughout the body. The "gold standard" test for diagnosis is a formal food challenge, in which increasing doses of food are given under medical supervision. However, food challenges are time-consuming, costly, and not without risk, due to the potential for inducing severe or even fatal anaphylaxis. In practice, IgE-mediated food allergy is usually diagnosed using a surrogate: the detection of specific IgE to the implicated food (called "sensitisation"), either in the skin (through skin prick testing) or blood. Unfortunately, these measures over-estimate the rate of true clinical allergy. In large, population-based studies, over 50% of those with a positive skin test to a food can eat that food without clinical symptoms ie. the antibody is present, but does not result in mast cell activation. The use of tests which assess sensitisation alone results in over-diagnosis, causing unnecessary dietary/social restrictions and anxiety which can impair nutrition and quality of life: the adverse impact of food allergy in children is greater than that caused by diabetes and other chronic illnesses. This, in turn, increases demand for food challenges which become necessary to clarify the diagnosis. Safer and less burdensome diagnostics which can be performed in the outpatient setting are therefore an important goal.In this proposal, we will assess the ability of 2 novel, complementary tests to accurately diagnose food allergy. We will recruit children and young people with indeterminate allergic status despite conventional allergy testing, who have been recruited from our specialist allergy clinic and are due to undergo formal food challenge to clarify a diagnosis of food allergy to peanut, egg or cow's milk.In addition to undertaking conventional allergy tests immediately prior to the food challenge, we will perform:1. Mast cell activation test - in which mast cells (generated from precursor cells in donated blood) are incubated with a small amount of blood from the patient and then exposed to the food allergen, and the mast cell response measured. Our pilot data indicates this is a robust test, with excellent ability to distinguish between true allergy and sensitisation alone.2. Intranasal food challenge - a quick and straightforward procedure in which very small amounts of food protein are administered into the nose, causing a mild hay fever-like response in allergic, but not non-allergic individuals. The technique is identical to that used for the intranasal influenza vaccine given in primary care as part of the UK National Immunisation Schedule. Feedback from participants who participated in a pilot study reported that they found the lack of clinical symptoms at intranasal challenge to be reassuring, reducing both their own and their families' concern over subsequently eating the food to demonstrate no clinical allergy.We will assess how these tests compare to conventional allergy testing, to determine the best strategy to accurately diagnose food allergy without the need for formal food challenge.Our preliminary data indicates that both techniques may confer significant diagnostic accuracy over existing allergy tests. This study will provide the necessary validation to secure follow-on translational funding and commercial investment, to accelerate product development through to regulatory approvals and, ultimately, clinical use. This will assist healthcare professionals in providing more accurate diagnoses, reassurance to patients and parents alike, as well as delivering economic savings to the NHS.

食物过敏是一个日益严重的公共卫生问题，在英国影响多达2%的成年人和6%的儿童。它是危及生命的过敏反应（过敏反应）的最常见原因。过敏反应是过敏原特异性免疫球蛋白E（IgE）抗体与食物过敏原之间相互作用的结果，导致免疫细胞（包括全身发现的肥大细胞）活化。诊断的“金标准”测试是一种正式的食物挑战，在这种测试中，在医疗监督下给予越来越多的食物。然而，食物挑战是耗时的，昂贵的，并且不是没有风险的，因为有可能诱导严重甚至致命的过敏反应。在实践中，IgE介导的食物过敏通常使用替代品进行诊断：检测皮肤（通过皮肤点刺试验）或血液中对相关食物的特异性IgE（称为“致敏”）。不幸的是，这些措施高估了真正的临床过敏率。在大规模的人群研究中，超过50%的皮肤试验阳性的人可以吃这种食物而没有临床症状。抗体存在，但不导致肥大细胞活化。使用单独评估致敏性的测试会导致过度诊断，造成不必要的饮食/社会限制和焦虑，从而损害营养和生活质量：食物过敏对儿童的不利影响大于糖尿病和其他慢性疾病造成的影响。这反过来又增加了对食品挑战的需求，这对于澄清诊断是必要的。因此，在门诊环境中进行更安全和更少负担的诊断是一个重要的目标。在本提案中，我们将评估2种新的互补测试准确诊断食物过敏的能力。我们将招募从我们的过敏专科诊所招募的儿童和青少年，他们在常规过敏测试中过敏状态不确定，并将接受正式的食物激发，以明确对花生、鸡蛋或牛奶食物过敏的诊断。除了在食物激发前立即进行常规过敏测试外，我们还将进行：1.肥大细胞活化试验-其中肥大细胞（从捐赠血液中的前体细胞产生）与少量患者血液一起孵育，然后暴露于食物过敏原，并测量肥大细胞反应。我们的试点数据表明，这是一个强大的测试，具有出色的能力，以区分真正的过敏和致敏单独。鼻内食物激发-一种快速而直接的程序，其中将非常少量的食物蛋白质注入鼻子，在过敏性个体中引起轻度干草热样反应，但在非过敏性个体中不会。该技术与作为英国国家免疫接种计划一部分的初级保健中鼻内流感疫苗所用的技术相同。参与一项试点研究的参与者的反馈报告说，他们发现鼻内激发时没有临床症状是令人放心的，减少了他们自己和家人对随后食用食物以证明没有临床过敏的担忧。我们将评估这些测试与传统过敏测试的比较，以确定最佳的策略，以准确地诊断食物过敏，而不需要正式的食物挑战。我们的初步数据表明，这两种技术可能会赋予显着的诊断准确性超过现有的过敏试验。这项研究将提供必要的验证，以确保后续的转化资金和商业投资，加速产品开发，直至获得监管批准，并最终进入临床使用。这将有助于医疗保健专业人员提供更准确的诊断，让患者和家长放心，并为NHS节省经济开支。

项目成果

Single-dose oral challenges to validate eliciting doses in children with cow's milk allergy.

单剂量口服挑战，以验证对牛奶过敏的儿童的诱发剂量。

• DOI: 10.1111/pai.13482
• 发表时间: 2021
• 期刊: official publication of the European Society of Pediatric Allergy and Immunology
• 作者: Turner PJ

Mast cell tissue heterogeneity and specificity of immune cell recruitment.

• DOI: 10.3389/fimmu.2022.932090
• 发表时间: 2022
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: West, Peter W.;Bulfone-Paus, Silvia
• 通讯作者: Bulfone-Paus, Silvia

Novel Approaches in the Inhibition of IgE-Induced Mast Cell Reactivity in Food Allergy.

• DOI: 10.3389/fimmu.2021.613461
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Tontini C;Bulfone-Paus S
• 通讯作者: Bulfone-Paus S

Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins.

• DOI: 10.3389/fimmu.2020.615236
• 发表时间: 2020
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: West PW;Bahri R;Garcia-Rodriguez KM;Sweetland G;Wileman G;Shah R;Montero A;Rapley L;Bulfone-Paus S
• 通讯作者: Bulfone-Paus S

Impact of using less objective symptoms to define tolerated dose during food challenges: A data-driven approach

使用不太客观的症状来定义食物挑战期间耐受剂量的影响：数据驱动的方法

• DOI: 10.1016/j.jaci.2022.12.818
• 发表时间: 2023
• 期刊: Journal of Allergy and Clinical Immunology
• 影响因子: 14.2
• 作者: Turner P