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Anti-IgE therapy

Thomas B Casale, MD
Section Editor
Bruce S Bochner, MD
Deputy Editor
Anna M Feldweg, MD


Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases, including asthma [1]. For this reason, IgE-mediated immunologic pathways have long represented an attractive target for therapeutic agents in asthma and other allergic diseases.

This review will examine IgE neutralization therapy with anti-IgE monoclonal antibody, with a focus on the treatment of asthma. Other promising approaches to reducing IgE, as well as investigational applications of anti-IgE to other disorders, will be discussed briefly. The role of anti-IgE therapy in the overall management of asthma, as recommended by national and international asthma guidelines, is presented separately. The use of anti-IgE in the management of chronic urticaria is also discussed in greater detail elsewhere. (See "An overview of asthma management" and "Chronic urticaria: Treatment of refractory symptoms", section on 'Omalizumab'.)


Most asthmatic patients have elevated circulating immunoglobulin E (IgE) concentrations when levels are adjusted for age [2]. Allergic sensitization results from the formation of specific IgE in response to common inhalant allergens, such as those derived from house dust mites, pollens, animal dander, molds, and cockroaches.

IgE is produced by B lymphocytes under the direction of two cytokines: interleukin-4 (IL-4) and the closely related interleukin-13 (IL-13), which are produced by several cell types including T helper type 2 (Th2) cells (a subset of T helper lymphocytes prevalent in atopy) [3,4]. IgE formation is markedly enhanced by the interaction of two costimulatory molecules: CD40 ligand expressed on Th2 cells and CD40 expressed on B cells. Appropriately stimulated B cells mature into plasma cells that secrete allergen-specific IgE, which circulates and binds to high-affinity receptors (Fc-epsilon-RI) on the surface of mast cells, basophils, and other cells. (See "Mast cells: Surface receptors and signal transduction", section on 'High affinity IgE receptor'.)

Bridging of IgE molecules on mast cells and basophils by protein allergens results in the activation of these cells. Activation leads to release of preformed mediators, such as histamine, and increased synthesis of lipid mediators, such as prostaglandins and cysteinyl-leukotrienes, which in turn results in bronchoconstriction and plasma exudation [5]. Subsequently, mast cells and basophils synthesize and release a number of cytokines important in allergic inflammation. Thus, IgE plays a central role in the mechanism of immediate bronchoconstriction and the late inflammatory response after allergen inhalation challenge of allergic asthmatic subjects. (See "The biology of IgE" and "The relationship between IgE and allergic disease".)


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