After the discovery ofhouse dust mites in 1964 their association with asthma has been reported from many different parts of the world including the developing countries. Two sets of major allergens from mites of the genus Dermatophagoides are now well recognized. The Group I allergens are glycoproteins of relative molecular mass (Mr) 25 000, which show both structural homology and cross-reactivity. The allergen Der p I has been cloned and sequenced confirming the M, and establishing its nature as a protease. The Group II allergens (Mr 15 000) show even closer homology and cross-reactivity.Specific immunoassays for Group I and Group II allergens, using monospecific antisera and monoclonal antibodies, have been standardized and are suitable for measuring allergen levels in different parts of the world.Measures for reducing the levels of mite allergens in houses include the covering of mattresses, hot washing of bedding, and removal of carpets from bedrooms as well as humidity control, vacuum cleaning, and the use ofacaricides in the rest ofthe house. There is already evidence that these procedures can cause a major improvement in the symptoms of asthma. While provisional standards for both sensitization to mites and also mite allergen exposure can now be recommended, there is an urgent needfor controlled studies using protocols demonstrated to reduce mite allergen levels by at least tenfold and for further international collaboration.

A very high prevalence of immediate hypersensitivity to common indoor allergens can be demonstrated among children and young adults, with asthma. Recent progress in the immunochemistry of cat, dust mite and cockroach allergens has made it possible to measure exposure to these allergens and to start to define threshold levels of exposure which increase the risk of sensitization and symptomatic asthma. Indeed, it is already clear that exposure to >2 μg group I dust mite allergen (or 100 mites) per gram of dust increases the risk of children developing sensitization and asthma. Furthermore, from studies on patients presenting to emergency rooms with asthma, it is clear that the risk of sensitization to allergens derived from cats or cockroaches or grass pollen is restricted to patients who are exposed to high levels of these allergens. Given the increasing morbidity and mortality of asthma it is clear that therapeutic efforts should be focused on identifying relevant allergens and advising patients about techniques for reducing exposure.

No abstract

Der p 2 is one of the most important allergens from the house dust mite Dermatophagoides pteronyssinus. Identification of human IgE Ab binding epitopes can be used for rational design of allergens with reduced IgE reactivity for therapy. Antigenic analysis of Der p 2 was performed by site-directed mutagenesis based on the x-ray crystal structure of the allergen in complex with a Fab from the murine IgG mAb 7A1 that binds an epitope overlapping with human IgE binding sites. Conformational changes upon Ab binding were confirmed by nuclear magnetic resonance using a 7A1-single-chain variable fragment. In addition, a human IgE Ab construct that interferes with mAb 7A1 binding was isolated from a combinatorial phage-display library constructed from a mite-allergic patient and expressed as two recombinant forms (single-chain Fab in Pichia pastoris and Fab in Escherichia coli). These two IgE Ab constructs and the mAb 7A1 failed to recognize two Der p 2 epitope double mutants designed to abolish the allergen-Ab interaction while preserving the fold necessary to bind Abs at other sites of the allergen surface. A 10-100-fold reduction in binding of IgE from allergic subjects to the mutants additionally showed that the residues mutated were involved in IgE Ab binding. In summary, mutagenesis of a Der p 2 epitope defined by x-ray crystallography revealed an IgE Ab binding site that will be considered for the design of hypoallergens for immunotherapy.

No abstract