Mechanisms of action of anti–immunoglobulin E therapy

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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: March 1, 2006

More about this publication?
  • Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.

    The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma.

    Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.

    Articles marked "F" offer free full text for personal noncommercial use only.

    The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
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