Mechanisms of action of anti–immunoglobulin E therapy
Abstract:The currently approved anti–immunoglobulin E (IgE) agent omalizumab is a humanized monoclonal antibody that recognizes human IgE in the vicinity of its binding sites for high- and low-affinity IgE receptors. Omalizumab binds free IgE and the complexes that are formed are removed by the hepatic reticuloendothelial system. Over time, IgE comes off its receptors on various cells (primarily basophils and mast cells), rendering these cells "nonfunctional," in that they lose their ability to respond to allergen. This process is enhanced by the fact that, as IgE receptors are freed, their numbers on cell surfaces decline. The kinetics of cellular defunctionalization may differ depending on the cell type (basophils are believed to lose IgE earlier), the number of cell-surface–specific IgE molecules before initiation of treatment, and the cellular sensitivity of individual patients. Inability to respond to allergen reduces acute allergic reactions and their inflammatory and physiological consequences such as late reductions in lung function and tissue eosinophilia. Chronic airway inflammation is suppressed also, but the effect on airway hyperresponsiveness is modest. A potential role of anti-IgE therapy to act as an immunomodulator by affecting antigen presentation through the removal of IgE from the surface of dendritic cells has not been explored. Also unknown is whether anti-IgE can bind to membrane-bound IgE on B lymphocytes and influence IgE production by these cells. Anti-IgE therapy has provided a strong proof of concept for the central role of the IgE system in asthma and other allergic diseases.
Document Type: Research Article
Publication date: 2006-03-01
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