Allergens in the pathogenesis of asthma: potential role of anti-immunoglobulin E therapy.
Evidence suggests that allergy is a significant triggering factor in asthma in children and adults alike. In immunoglobulin (Ig) E-mediated allergic reactions, sensitization occurs when allergen-specific B cells are stimulated and switched to IgE antibody production by interleukin (IL)-4 and IL-13 provided by helper T cells type 2 (Th2). The IgE antibodies act by arming cells bearing either the high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII or CD23) receptor. The subsequent interaction of allergen with IgE-FcepsilonRI complexes on mast cells and basophils causes cross-linking of receptors that triggers the release of a variety of inflammatory mediators, cytokines and chemokines. Therefore, the ability to lower circulating free IgE levels is desirable because most individuals are exposed to multiple allergens to which they are sensitive at any given time. Omalizumab (formerly known as rhuMAb-E25) is a recently developed humanized monoclonal anti-IgE antibody directed at the FcepsilonRI binding domain of human IgE. It inhibits binding of IgE to mast cells without provoking mast cell activation. Preliminary clinical data from randomized controlled trials have shown that the addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use. The compound is also well tolerated. Omalizumab represents a novel therapeutic approach in the management of asthma.
Storms
William
W
University of Colorado Health Sciences Center, Colorado Springs, Colorado, USA. sneezedoc@aol.com
D000485:Allergens / Q000276:immunology*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D000069444:Omalizumab
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D000069444:Omalizumab