The purpose of this research is to more precisely define the prevalence, natural history, and immunopathogenic mechanisms of food hypersensitivity (FH) in children with atopic dermatitis (AD). Studies of dietary prophylaxis in newborns at high risk for atopic disease and provocation of skin symptoms and immunologic changes by blinded food challenges strongly suggest a significant pathogenic role for IgE-mediated FH in AD. Recent evidence indicates that surface-bound IgE molecules may function as receptors on a variety of antigen presenting cells (APC's) and effector cells. In the presence of allergen, these cells are activated to release mediators and cytokines, which lead to expression of local endothelial adhesion molecules, recruitment of inflammatory cells, and perpetuation of inflammation. Patients with AD and FH provide a unique human model to study the controlled interaction between allergen and host. The majority of dermatologists agree that IgE-mediated FH occurs in some children with AD, but argue that it is rare and has little significance in the pathogenesis of AD. Proposed studies will define the prevalence of FH in children with AD attending a typical dermatology clinic and establish the efficacy of food allergen elimination in a blinded treatment trial of patients with AD and FH. Conclusive studies would have a major impact on """"""""standard care"""""""" of AD in children. The applicant has shown that food allergen elimination leads to resolution of eczema in many food allergic patients and eventual loss of allergen-specific clinical reactivity (""""""""clinical tolerance""""""""). The applicant believes that allergen elimination may lead to loss of responsiveness of allergen-specific TH2-type cells bearing the """"""""cutaneous lymphocyte antigen (CLA) homing receptor,"""""""" B cells and APC's, probably due to a decrease in allergen-specific CLA+ TH2 and B cell frequency, and decrease in APC surface-bound allergen-specific IgE. In this proposal, responses of circulating and lesional T cells to food allergens and IgE-dependent activation of monocytes will be characterized. Longitudinal studies will examine changes in T cell and monocyte responses associated with the development of clinical food tolerance. Since egg hypersensitivity is seen in two-thirds of AD patients with FH, B cell and T cell epitopes of ovomucoid, the dominant egg allergen, will be elucidated. Reactivity of both IgE antibodies and T cells to these peptides will be examined before and after the development of clinical tolerance. These studies will provide insight into immunopathogenic mechanisms of food-induced eczema and delineate immunologic changes associated with the resolution of clinical reactivity. Food-induced eczema provides an excellent model of allergen-induced inflammation, which may provide a better understanding of other allergic disorders and lead to the development of safer forms of immunomodulation.
Showing the most recent 10 out of 73 publications
