Project Summary Food allergy is a common disease that affects up to 15 million Americans. Although clinically there appears to be a wide spectrum of disease, sub-types of food allergy with different clinical courses, co-morbidities and responses to therapy have not been systematically identified. Identifying such sub-types of food allergy will allow for tailored care of food allergic individuals. A second major research gap is our understanding of the absolute risk and predictors of serious allergic reactions among those with food allergy who are receiving high quality medical care. Establishing the risk and predictors of serious reactions will have critical implications for determining the risk:benefit ratio for food allergy treatments, educating patients, identifying targets for reducing risk, and determining the best candidates for treatment. This proposal is create a large repository, biobank and prospective observational study of food allergic patients by enrolling 2000 subjects with IgE mediated milk, egg or peanut allergy. Sub-types of food allergy will be identified using unsupervised methods based on comprehensive clinical and immunologic data. The rate of reactions to foods will be closely monitored using innovative mobile health technology. In addition to those major goals, the infrastructure created in this observational cohort through the formation of a registry of well phenotyped food allergic patients and the development of methods to monitor reactions will enable subsequent clinical trials funded by CoFAR to recruit and proceed efficiently, and will provide samples for the opportunity fund. The specific aims of this project are: (1) To establish a large registry and biobank of subjects with milk, egg and/or peanut allergy, (2) To establish phenotypes of food allergy by clinically and immunologically characterizing food allergic individuals (Aim 2A) and to identify predictors of these phenotypes (Aim 2B), and (3) To establish the rate of food allergic reactions among individuals with food allergy (Aim 3A) and determine predictors of reaction frequency and severity (Aim 3B). The results of these investigations will help inform clinical care of food allergic individuals by allowing for tailored care of food allergic individuals, and by informing the risk:benefit ratio for food allergy treatments. This project will also critically advance research into food allergy by providing a registry from which to recruit patients for CoFAR, data on phenotypes which can be used to shape future clinical investigations, and data on predictors of reaction rates which can be used to design novel interventions.