Anti-IgE therapy in asthma: rationale and therapeutic potential.
Airway inflammation is found in virtually all individuals with asthma symptoms. The factors contributing to asthma-related airway inflammation are multiple and involve a number of different inflammatory cells and mediators. Allergic responses at the level of the respiratory system are mostly mediated by IgE-dependent mechanisms. After sensitization of a susceptible individual and the synthesis and binding of allergen-specific IgE to target cells, atopic individuals respond immunologically to common, naturally occurring allergens by releasing mast cell-derived mediators. Subsequent allergen exposure in susceptible individuals produces a characteristic cascade of events orchestrated by immune effector cells, most prominently, mast cells, T lymphocytes and eosinophils. A new strategy, neutralizing IgE antibodies, inhibits expression of allergic symptoms by preventing the initial trigger of the allergic reaction, IgE binding to IgE-receptor bearing cells. rhuMAb-E25 is a recombinant humanized monoclonal anti-IgE antibody currently under investigation that has been shown to reduce allergic responses in atopic individuals and to improve symptoms and reduce rescue medication and corticosteroid use in patients with allergic asthma. Thus, the clinical effectiveness of rhuMAb-E25 supports the central role of IgE in allergic reactions and the viability of anti-IgE therapy as a potentially effective treatment option for asthma.
Barnes
P J
PJ
National Heart and Lung Institute, London, UK. p.j.barnes@ic.ac.uk
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D002648:Child; D002986:Clinical Trials as Topic; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use
D000485:Allergens; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; C401983:rhuMAb-E25; D007073:Immunoglobulin E