MRC Transition Support CSF Alexandra Santos

MRC 过渡支持 CSF Alexandra Santos

• 批准号: MR/T032081/1
• 负责人: Alexandra Santos
• 金额: $ 84.5万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT032081%2F1
• 关键词: MRC; Transition; Support; CSF; Alexandra

The symptoms of food allergy (FA) result from the release of certain substances by cells of the immune system, called mast cells and basophils, triggered by the interaction between allergy antibodies (called IgE) and food allergens. FA is often diagnosed using skin prick test or by detecting IgE (allergy antibodies) in the blood. However, more common than being food allergic is to have a positive allergy test to that food. For example, only 1 out of 5 children with a positive allergy test to peanut in the United Kingdom has peanut allergy. In the equivocal cases (more than 50% of patients), an oral food challenge (OFC) is required. OFC consists in giving the patient the suspected food in a controlled environment to see whether the patient develops an allergic reaction. OFC are quite expensive, time-consuming and place the patient at risk of a potentially severe reaction, but this is currently the gold-standard for the diagnosis of FA.Funded by the MRC, I developed a new blood test called the basophil activation test (BAT) that works like an OFC in a test tube in the sense that allergen is added to cells in blood rather than food to the potentially allergic child, sparing patients from experiencing an allergic reaction. BAT to peanut showed 97% accuracy in the diagnosis of peanut allergy and reduced the need for OFC by two thirds. More recently, I have developed the BAT to cow's milk, egg, sesame and cashew nut and we are now assessing how useful BAT is to diagnose milk and egg allergies, which are the most common food allergies in childhood, and cashew and sesame allergies, which are two of the foods that most commonly require OFC as conventional allergy tests fail to diagnose allergy correctly. For this, we are inviting children with suspected food allergies to participate into the BAT 2 study, which is currently underway. Because BAT requires the use of fresh blood cells thus I developed a test similar to BAT using cells that are grown in the laboratory and thus are readily available - this is called the mast cell activation test (MAT). We have tested various samples of peanut allergic and non-allergic patients and showed that MAT confirms peanut allergy with a high degree of certainty. I anticipate that BAT and MAT will lead to a significant improvement of care for allergic patients and will reduce the costs and anxiety associated with OFC. Due to reasons beyond my control, there were some delays in the start and in recruiting to the BAT2 Study and the Transition Support would allow me to complete the study and obtain evidence to support advancing the development of these tests for clinical use.To understand why some patients have a positive allergy test and are not allergic, we have been studying the antibodies of allergic and non-allergic children. We have shown that the IgE of allergic patients has different characteristics from the IgE of non-allergic subjects and that non-allergic subjects who have the allergy antibodies tend to have blocking antibodies to counteract the IgE. We would now like to understand why the immune system of allergic and non-allergic subjects responds differently to food allergens in the first place, and will be testing samples that have been collected from participants in the BAT 2 study. By comparing the responses of T cells (which are the coordinators of the immune system) between allergic and non-allergic patients and between allergens that are known to cause life-long allergies with allergens that cause allergies that typically resolve, we will improve our understanding of why some children are allergic and others not, may find ways to turn off the allergic response and identify new targets for a curative treatment for FA. The MRC Transition Support would enable be to gather experimental data to support a future Senior Fellowship Application to explore these mechanisms in the future.

食物过敏 (FA) 的症状是由免疫系统细胞（称为肥大细胞和嗜碱性粒细胞）释放某些物质引起的，这些物质是由过敏抗体（称为 IgE）和食物过敏原之间的相互作用触发的。 FA 通常通过皮肤点刺试验或检测血液中的 IgE（过敏抗体）来诊断。然而，比食物过敏更常见的是对该食物进行过敏测试呈阳性。例如，在英国，花生过敏测试呈阳性的儿童中，只有五分之一患有花生过敏。对于模棱两可的病例（超过 50% 的患者），需要进行口服食物挑战 (OFC)。 OFC 包括在受控环境中向患者提供可疑食物，以观察患者是否出现过敏反应。 OFC 非常昂贵、耗时，并且使患者面临潜在严重反应的风险，但这是目前诊断 FA 的黄金标准。在 MRC 的资助下，我开发了一种称为嗜碱性粒细胞活化测试 (BAT) 的新血液测试，其工作原理类似于试管中的 OFC，因为过敏原被添加到血液中的细胞中，而不是添加到潜在过敏儿童的食物中，从而使患者免受过敏反应。针对花生的 BAT 在花生过敏诊断中显示出 97% 的准确率，并将 OFC 的需求减少了三分之二。最近，我开发了针对牛奶、鸡蛋、芝麻和腰果的最佳可行技术，我们现在正在评估最佳可行技术对于诊断牛奶和鸡蛋过敏（这是儿童期最常见的食物过敏）以及腰果和芝麻过敏（这两种最常需要 OFC 的食物，因为传统过敏测试无法正确诊断过敏）的有用性。为此，我们邀请疑似食物过敏的儿童参加目前正在进行的 BAT 2 研究。由于 BAT 需要使用新鲜血细胞，因此我开发了一种类似于 BAT 的测试，使用实验室中生长的细胞，因此很容易获得 - 这称为肥大细胞激活测试 (MAT)。我们测试了花生过敏和非过敏患者的各种样本，结果表明 MAT 可以高度确定地确认花生过敏。我预计 BAT 和 MAT 将显着改善过敏患者的护理，并减少与 OFC 相关的费用和焦虑。由于我无法控制的原因，BAT2 研究的启动和招募出现了一些延误，过渡支持将使我能够完成研究并获得证据来支持推进这些测试的临床应用的开发。为了了解为什么有些患者的过敏测试呈阳性但并不过敏，我们一直在研究过敏和非过敏儿童的抗体。我们已经证明，过敏患者的 IgE 与非过敏受试者的 IgE 具有不同的特征，并且具有过敏抗体的非过敏受试者往往具有阻断抗体来抵消 IgE。我们现在想首先了解为什么过敏和非过敏受试者的免疫系统对食物过敏原的反应不同，并将测试从 BAT 2 研究参与者收集的样本。通过比较过敏和非过敏患者之间以及已知会导致终生过敏的过敏原与通常会消退的过敏原之间的 T 细胞（免疫系统协调员）的反应，我们将加深对为什么有些儿童过敏而另一些儿童不过敏的理解，可能找到关闭过敏反应的方法，并确定 FA 治疗的新靶点。 MRC 过渡支持将使我们能够收集实验数据，以支持未来的高级奖学金申请，以在未来探索这些机制。

项目成果

Oral Tolerance Induction-Opportunities and Mechanisms.

• DOI: 10.3390/foods11213386
• 发表时间: 2022-10-27
• 期刊: Foods (Basel, Switzerland)

Biomarkers to predict changes in peanut allergy in children over time

预测儿童花生过敏随时间变化的生物标志物

• DOI: 10.22541/au.169967226.62811705/v1
• 发表时间: 2023
• 作者: Foong R

Editorial comments on: "Immune-related microRNAs in breast milk and their relation to regulatory T cells in breastfed children".

编辑评论：“母乳中的免疫相关 microRNA 及其与母乳喂养儿童的调节性 T 细胞的关系”。

• DOI: 10.1111/pai.13958
• 发表时间: 2023
• 期刊: official publication of the European Society of Pediatric Allergy and Immunology
• 作者: Eigenmann P