MRC Transition Support CSF Alexandra Santos

点击翻译按钮获取中文摘要

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.