This research is designed to explore basic mechanisms involved in IgE-mediated reactions to foods and their potential role in the pathogenesis of atopic dermatitis (AD). Studies over the past 3 years have identified 63/113 children with severe AD who developed immediate hypersensitivity reactions following double-blind placebo-controlled food challenges (DBPCFC); 84% of positive responses involved cutaneous symptoms consisting of a markedly pruritic, erythematous macular or morbilliform rash. A significant rise in plasma histamine was demonstrated only in a group of patients experiencing positive oral challenges, thus implicating mast cell/basophil involvement in the pathogenesis of food-induced symptoms. Abstinence from the offending food has led to significant improvement in most children and a loss of hypersensitivity after 1-2 years on 60% (18/30) cases. Proposed studies will continue to evaluate the natural history of food hypersensitivity in children with AD. Using AD patients with food hypersensitivity diagnosed by DBPCFC, potential pathogenic mechanisms will be sought: 1) changes in skin histamine, eosinophil major basic protein, and arachidonic acid metabolites, as measured in skin blister fluid; 2) abnormal gut permeability, as defined by increased antigenemia; and 3) possible aberrant gut-associated and systemic immunological responses. The effects of prolonged antigen restriction on the resolution of food hypersensitivity, eczematoid rash, and concomitant changes in gut and systemic immunological parameters will be evaluated. Standard diagnostic procedures (skin testing, RAST, antigen-specific IgG) and others (EILSA assays developed for detecting circulating food antigens, serum and salivary antigen-specific IgA, and crossed-radioimmunoelectrophoresis developed with 125I labelled anti-human IgE, IgA, and IgG, spontaneous basophil histamine release, spontaneous and antigen-induced lymphocyte production of """"""""histamine-releasing activity"""""""") will be examined for their usefulness in detecting and following clinically significant food allergy as defined by DBPCFC. In addition, the antigenic determinants of two major allergens, ovalbumin and B-lactoglobulin, will be characterized using a panel of monoclonal antibodies and evaluated for allergenicity. Digestibility of various food antigens will be assessed using an immobilized digestive enzyme system and the allergenicity of these breakdown products evaluated using sera from patients sensitive to specified foods.
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