EVALUATION OF BASOPHIL INVOLVEMENT IN HUMAN DISEASE

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DESCRIPTION (Adapted from Investigator's abstract): Basophils and mast cells are major effector cells of immediate hypersensitivity reactions. In humans, mast cell involvement can be precisely identified by the presence of tryptase. For basophils, no such direct marker has been identified. The investigator hypothesizes that human basophil secretory granule proteins can be used as sensitive and specific markers of basophil involvement and that understanding the functions of such proteins will further our understanding of this cell type. The 2D7 mAb prepared by the investigator appears to recognize a basophil-specific component of the secretory granule. In skin during the late phase of an immediate hypersensitivity response, 2D7 immunohistochemistry reveals marked basophil involvement. Four specific aims are proposed. First, the 2D7 antigen will be purified by immunoaffinity chromatography and characterized. Second, basophils and deposits of activated basophils will be examined in human tissues using the 2D7 mAb, including skin in atopic dermatitis, chronic urticaria, and urticaria pigmentosa, nasal mucosa in allergic rhinitis and lung in asthma. Third, new mAbs against 2D7 antigen will be generated and used to develop a sandwich immunoassay. Fourth, basophil activation in various clinical situations will be assessed by measuring 2D7 antigen levels in biologic fluids. For example, the investigator hypothesizes that basophil-dependent anaphylaxis occurs in certain food-allergic reactions, and predict that 2D7 antigen, but not mast cell tryptase, will be elevated in the blood during such reactions. This research will provide novel and precise measures of basophil involvement in human diseases. This may enable more precise diagnostic criteria for flares of inflammation associated with atopic disease, facilitate selection of appropriate treatment, provide new prognostic information, and permit monitoring of inflammatory disease activity.