Novel Treatment Strategies in IgE-Mediated Allergy
Prof. Dr. U. Wahn
Department for Pediatric Pneumology and Immunology
Charité, Humboldt-Universität, Berlin
A key feature of allergic airway disease is the exaggerated immune response to a causal allergen, resulting in the overproduction of allergen specific IgE antibodies, and a raised serum IgE level. IgE binds avidly to FcєRI receptors expressed predominantly on mast cells and basophils. Free IgE has a short half life of two days before it is selectivly degraded in endosomes. Therefore free IgE is a possible target for removal by an anti-IgE antibody. Since IgE is initiating the inflammatory cascade, it is a candidate target molecule for immunotherapeutic interventions.
During the last years recombinant monoclonal murine antibodies, which have been humanized, were developed, which have the capacity to prevent IgE molecules from binding to high affinity receptors without stimulating mast-cell degranulation. Omalizumab, a humanized monoclonal antibody, which contains only 5 % of non-human residues, has been extensively studied in allergic patients with asthma as well as allergic rhinitis. It represents a first therapeutic agent to bind free IgE and inhibit mast-cell degranulation, representing a novel approach to the control of IgE-mediated diseases.
In studies with adult and pediatric asthma populations, Omalizumab has been demonstrated to reduce the need for topical as well as systemic corticosteroids and prevent asthma exazerbations. Trials with patients suffering from seasonal allergic rhinoconjunctivits demonstrated that Omalizumab has the potential to reduce allergic symptoms of the upper airways and the need foe rescue medication.
In a recent study on children with sensitization to birch and grass pollen and seasonal allergic rhinoconjunctivitis it could be demonstrated that Omalizumab provides an additional reduction of symptom scores and the usage of rescue medication over specific immunotherapy alone. Therefore Anti-IgE treatment might be a future therapeutic option for allergic patients with multiple allergies.
Whether the application of anti-IgE is able to alter the long-term history of allergic airway diseases, remains to be shown.
Fick B. Anti-IgE as a novel therapy for the treatment of asthma. Curr Opin Immunol 1999;5;76-80
Chang T. the pharmacological basis of anti-IgE therapy. Nat Biotechnol 2000; 18; 157-62
Kuehr J, Brauburger J, Zielen S, Schauer U, Kamin W, von Berg AS. Leupold W, Bergmann KC, Rolinck-Werninghaus C, Gäve M, Hultsch Th, Wahn U. Efficacy of combinant treatment with anti-IgE specific immunotherapy in polysensitized children and adolescent with seasonal allergic rhinitis. JACI 109 (2), 274-280