Northwestern University CoFAR (NU-CoFAR) Clinical Research Center - Food allergy is a common disease with few treatment options, and although life-threatening reactions are very rare, the lack of predictability of reaction severity contributes to a significant negative impact on quality of life. Studies are needed to test new therapies, identify new targets through mechanistic research, and to advance the understanding of key clinical parameters including severity, threshold, and prognosis for allergy resolution. There is also a need to identify and rectify disparities in access to care and representation in research, an area in which we have made significant contributions. As a first aim, a clinical research center – NUCoFAR- will be established at Northwestern University using the expertise of investigators at the Lurie Children’s Hospital, Feinberg School of Medicine, and the Center for Food Allergy and Asthma Research. These experts will recruit children and adults with food allergy for observational or intervention studies, as well as pregnant women and infants for prevention studies, and carry out human studies using best practices. Since food allergy exhibits the characteristics of a complex genetic trait, it is imperative that research aiming to understand its etiology can leverage large, heterogeneous patient populations, beyond those available at any single institution. Consequently, the current understanding of this complex trait can be greatly advanced by systematically combining data across multiple clinical research centers. A standard approach for doing this is the creation of a data commons- a single, centralized resource that supports harmonized data aggregation and access from disparate sources, in accordance with FAIR (Findable, Accessible, Interoperable, and Reusable) principles. In a second aim, the CoFAR network will develop and populate a Food Allergy Data Commons (FADC) that will facilitate network-wide data sharing and collaboration across numerous priority research domains. We are partnering with leaders in the informatics field to advance this aim. NUCoFAR will work with other CoFAR Clinical Research Centers to develop efficient data upload procedures to the FADC. This access to standardized, structured data will allow the community of CoFAR researchers to answer critical research questions around food allergy development, diagnosis, progression, severity, and potential for natural tolerance. To advance the understanding of basic mechanisms of food allergy and oral tolerance, a third aim will identify the role of T cell-B cell interactions resulting in tolerance from early allergen introduction. This project will use biospecimens obtained by the CAN DO study, a multi-site clinical trial testing the impact of introduction of eight allergens into the diet by nine months of age on the development of food allergy. The contribution of T follicular helper (Tfh) cells and Type 2-marked memory B cells (MBC2) to the development of allergy and tolerance to foods will be tested. By elucidating the immune mechanisms responsible for the window of opportunity for oral tolerance development, these studies will identify novel pathways that could be targeted therapeutically to help children and adults with established food allergy.
