The purpose of this research is to study the natural history, immunopathophysiology, and potential diagnostic and therapeutic modalities of IgE-mediated food hypersensitivity in patients with atopic dermatitis. In the past 6 years, we have studied 204 children with severe atopic dermatitis for food hypersensitivity utilizing double-blind placebo controlled oral food challenges (DBPCFC). Sixty-two percent of patients reacted to one or more foods, 80% of which involved the skin. Activation of IgE- sensitized mast cells by ingested food antigen was suggested by a rapid rise in plasma histamine, and no significant change in C3a, C5a, and/or total blood basophil histamine content or number. Abstinence from the offending food led to significant improvement in eczematous symptoms and loss of symptomatic sensitivity in 1/3 of children within 2-3 years. Proposed studies will define the long-term natural history of food hypersensitivity in patients with atopic dermatitis. Patients will be studied for changes in intestinal permeability to protein, in quantities of food antigen-specific secretory IgA, types of circulating immune complexes, relative affinity of food specific antibodies, and releasability of basophils and cutaneous mast cells in an attempt to understand why some patients develop and later """"""""out-grow"""""""" food allergies. Patients with food hypersensitivity have been shown to have high """"""""spontaneous'' basophil histamine release in vitro and to ''spontaneously"""""""" produce a histamine- releasing factor (HRF) from cultured mononuclear cells. Circulating basophil and skin mast cell """"""""releasibility"""""""" will be evaluated with antigen-specific and non-specific stimuli to determine whether increased """"""""spontaneous"""""""" basophil histamine release reflects any underlying defect in these patients and whether food allergen avoidance leads to decreased basophil and/or skin mast cell releasibility. The mononuclear cell HRF will be characterized and evaluated for its ability to recognize different types of IgE molecules. Whether """"""""spontaneous"""""""" generation of HRF correlates with clinical reactivity and/or basophil releasibility and whether it can be stimulated in vitro by antigen exposure will be examined. Skin blister chambers will be placed in patients undergoing repeat DBPCFC's to demonstrate that cutaneous late-phase reactions occur following food ingestion and to determine which inflammatory mediators are released into the skin and therefore may be involved in the immunopathogenic events leading to eczematous skin changes.
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