MRC Transition Support CSF Alexandra Santos

食物过敏（FA）的症状是由免疫系统的细胞（肥大细胞和嗜碱性细胞）释放某些物质引起的，这些物质是由过敏抗体（IgE）和食物过敏原之间的相互作用引发的。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这种食物的过敏测试呈阳性。例如，在英国，对花生过敏测试呈阳性的儿童中，只有五分之一对花生过敏。在模棱两可的情况下（超过50%的患者），需要口服食物挑战（OFC）。OFC包括在受控环境中给予患者可疑食物，以观察患者是否产生过敏反应。OFC非常昂贵，耗时，并使患者面临潜在严重反应的风险，但这是目前诊断FA的金标准。在MRC的资助下，我开发了一种新的血液测试，叫做嗜碱性粒细胞激活测试（BAT），它的工作原理就像试管中的OFC一样，它将过敏原添加到血液细胞中，而不是添加到潜在过敏儿童的食物中，从而使患者免于过敏反应。在花生过敏的诊断中，BAT显示97%的准确率，并将OFC的需求减少了三分之二。最近，我开发了牛奶，鸡蛋，芝麻和腰果的BAT，我们现在正在评估BAT对诊断牛奶和鸡蛋过敏的有用程度，这是儿童最常见的食物过敏，以及腰果和芝麻过敏，这是两种最常需要OFC的食物，因为传统的过敏测试不能正确诊断过敏。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，使用在实验室中培养的细胞，因此很容易获得——这被称为肥大细胞激活测试（MAT）。我们对花生过敏和非过敏患者的各种样本进行了测试，结果表明MAT高度肯定地证实了花生过敏。我预计BAT和MAT将显著改善对过敏患者的护理，并降低与OFC相关的成本和焦虑。由于我无法控制的原因，在开始和招募BAT2研究时出现了一些延迟，过渡支持将允许我完成研究并获得证据，以支持推进这些测试的临床应用。为了理解为什么有些患者过敏试验呈阳性而不过敏，我们一直在研究过敏儿童和非过敏儿童的抗体。我们已经证明过敏患者的IgE与非过敏人群的IgE有不同的特征而非过敏人群中有过敏抗体的人往往会有阻断抗体来中和IgE。我们现在想了解为什么过敏和非过敏受试者的免疫系统首先对食物过敏原的反应不同，并将测试从BAT 2研究的参与者那里收集的样本。通过比较T细胞（免疫系统的协调者）在过敏和非过敏患者之间的反应，以及已知会导致终身过敏的过敏原与通常会导致过敏的过敏原之间的反应，我们将提高我们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过渡支持将使他能够收集实验数据，以支持未来的高级奖学金申请，以探索未来的这些机制。

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.