Understanding the Binding of IgE to Its High-Affinity Receptor and to an Anti-IgE Antibody

It has long been recognized that IgE-mediated secretion from tissue mast cells or circulating basophils is a central pathophysiological mechanism responsible for the signs and symptoms of allergic diseases. It has also been recognized that elimination of IgE antibody from the circulation should ameliorate the pathophysiological process associated with atopy. Of course, not all aspects of allergic diseases have been shown to be fully dependent on IgE-mediated function in mast cells and basophils, but even in the case of asthma, where a wide variety of pathophysiological mechanisms probably play a role in the expression of the disease, eliminating the IgE-mediated component should have marked effects on the symptoms and severity of the disease. The trick has been developing a therapeutic that reduces circulating IgE and then providing enough of the agent to chronically and markedly influence the functional responses of IgE-bearing cells. This is not an easy task because these cells are exquisitely sensitive to stimulation. A great deal of knowledge about basophil and mast cell function can be used to make predictions about the requirements for new IgE-suppressing therapeutics. Such therapeutics, if actually demonstrated to suppress circulating IgE and associated cellular responses, could be useful tools for dissecting out the relative roles 40of this arm of the immune response in a variety of atopic diseases, including asthma. A variety of schemes have been proposed to induce a decrease in circulating IgE; one currently undergoing investigation is monoclonal anti-IgE antibody. Coupled with recent knowledge about basophil and mast cell function, studies using anti-IgE antibody in vivo have provided useful insights into the nature of allergic reactions, the cell biology of the high-affinity receptor for IgE (FcεRI), and their relationship to studies of basophil and mast cell function.