Molecular and cellular targets of anti‐IgE antibodies

• Published in: Allergy (Copenhagen) 2005-08, Vol.60 (8), p.977-985
• Main Authors: Inführ, D., Crameri, R., Lamers, R., Achatz, G.
• Format: Article
• Language: English
• Subjects: Allergic diseases; Antibodies, Anti-Idiotypic - immunology; Antibodies, Anti-Idiotypic - therapeutic use; anti‐IgE antibody; apoptosis; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biological and medical sciences; B‐cell receptor; Cell Membrane - metabolism; Clonal Anergy; Down-Regulation; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Hypersensitivity - blood; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Immune Tolerance; Immunoglobulin E - metabolism; Immunopathology; Medical sciences; mIgE
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2005.00832.x

Immunoglobulin E (IgE) was the last of the immunoglobulins discovered. It is present in very low amounts (nano‐ to micro‐gram per ml range) in the serum of normal healthy individuals and normal laboratory mouse strains and has a very short half‐life. This contrasts with the other immunoglobulin classes, which are present in much higher concentrations (micro‐ to milligram per ml range) and form a substantial component of serum proteins. Immunoglobulins play a role in homeostatic mechanisms and they represent the humoral arm of defence against pathogenic organisms. Since IgE antibodies play a key role in allergic disorders, a number of approaches to inhibit IgE antibody production are currently being explored. In the recent past the use of nonanaphylactic, humanized anti‐IgE antibodies became a new therapeutic strategy for allergic diseases. The therapeutic rational beyond the idea derives from the ability of the anti‐IgE antibodies to bind to the same domains on the IgE molecule that interact with the high‐affinity IgE receptor, thereby interfering with the binding of IgE to this receptor without cross‐linking the IgE on the receptor (nonanaphylactic anti‐IgE antibodies). Treatment with anti‐IgE antibodies leads primarily to a decrease in serum IgE levels. As a consequence thereof, the number of high‐affinity IgE receptors on mast cells and basophils decreases, leading to a lower excitability of the effector cells reducing the release of inflammatory mediator such as histamine, prostaglandins and leukotrienes. Experimental studies in mice indicate that injection of some monoclonal anti‐IgE antibodies also inhibited IgE production in vivo. The biological mechanism behind this reduction remains speculative. A possible explanation may be that these antibodies can also interact with membrane bound IgE on B cells, which could interfere the IgE production.