Grant: CIHR Fellowship

Food protein induced enterocolitis syndrome (FPIES) is a type of food allergy resulting in severe vomiting 1-4h after ingestion of a trigger food. There are no treatments aside from allergen avoidance and fluid replacement after accidental ingestion. The underlying cause and immune mechanisms of FPIES remain unclear. We hypothesize that in FPIES, tissue-resident, food-specific T cells mediate symptoms. This is due to the delayed yet reproducible response to a particular food, evidence of T cell activation through cytokine measurements in blood, and the lack of food-specific T cells in circulation. Blood samples from FPIES patients (N=72) will be collected before and after a multi-day, low-dose oral food challenge (OFC). This prolonged allergen exposure is expected to liberate food-specific T cells from gastrointestinal tissues, as observed in celiac disease, where gluten-specific T cells are only detected after an extended period of controlled gluten ingestion. The immune cells will be analyzed using spectral flow cytometry and the activated cells will be sorted for single cell sequencing. The aims of this study are 1) to determine if food-specific T cells are activated following the OFC and 2) to identify the genes expressed by the activated cells. This study will add to the limited existing knowledge on this understudied disease. With access to human biospecimens from this rare and unique cohort, we will determine which food-specific immune cells cause gastrointestinal symptoms in FPIES. Identification of these cells and the immune basis of this disease may help in the development of treatment options. This will also provide insight into other food triggered intestinal diseases including other forms of food allergy and irritable bowel syndrome.