Molecular aspects of allergy

Atopic diseases such as asthma, rhinitis, eczema and food allergies have increased in most industrialised countries of the world during the last 20 years. The reasons for this increase are not known and different hypotheses have been assessed including increased exposure to sensitising allergens or decreased stimulation of the immune system during critical periods of development. In allergic diseases there is a polarisation of the Th2 response and an increase in the production of type 2 cytokines which are involved in the production of immunoglobulin E and the development of mast cells, basophils and eosinophils leading to inflammation and disease. The effector phase of atopy is initiated by interaction with FcERI expressed on effector cells such as mast cells and basophils but also found on an ever increasing list of cells. Binding of a polyvalent allergen to the variable part of IgE leads to a cross-link of the receptor that triggers the cell to release histamine and pharmacological mediators of the symptomatic allergic response. Cross-linking of FcERI by autoantibodies against the a -chain of the FcERI, causing subsequent histamine release is thought to be involved in the pathogenesis of other diseases such as chronic idiopathic urticaria (CIU). To date, most therapeutic strategies are aimed at inhibiting and controlling components of the inflammatory response. Recently, new treatment strategies have emerged that focus on the development of preventive and even curative treatments. The most promising therapeutic approaches are aimed at inhibiting the IgE FcERI interaction with the use of non-anaphylactogenic anti-IgE or anti-FcERIa autoantibodies. Clinical trials in humans using an humanised anti-IgE antibody showed that this antibody was well tolerated and reduced both symptoms and use of medication in asthma and allergic rhinitis. Thus interruption of the atopic cascade at the level of the IgE FcERI interaction with the use of non-anaphylactogenic antibodies is effective and represents an attractive therapy for the treatment of atopic disease. (C) 2002 Elsevier Science Ltd. All rights reserved.