Allergy is a specific, acquired immune response to a non-pathogenic antigen - the allergen - leading to hypersensitivity associated with clinical symptoms such as rhinitis or asthma. Type I hypersensitivity reactions, which occur immediately after exposure of an allergic person to the allergen, are based on the formation of specific immunoglobulin E (IgE) antibodies against common, environmental substances, e.g. pollens of trees, grasses and weeds, house dust mites, mould spores or animal dander.
Most allergens are soluble proteins or glycoproteins with a molecular weight between 5-70 kDa. Atopic persons are genetically predisposed to produce elevated levels of serum IgE which results in an increased risk for Type I reactions. The prevalence of atopic allergy has markedly increased over the course of the past two generations and allergic rhinitis, atopic asthma and atopic dermatitis represent an important cause of morbidity and impaired quality of life today. Besides a genetic predisposition, this development might be due to the higher hygiene standards and increased public health. Progressive changes in the Western life style, e.g. the use of antibiotics, diet and prophylactic immunization, seem to have affected the immune responsiveness of the population of industrialized countries and a larger number of individuals develop immediate hypersensitivity. Therefore, the need for an accurate diagnosis as well as effective treatments for allergic diseases has tremendously increased.
DIAGNOSIS AND THERAPY OF ALLERGIC DISEASES:
Diagnosis of Type I allergy is based on the detection of allergen-specific IgE antibody levels in the serum and on in vivo provocation tests with the respective allergens, e.g. skin prick tests. Current diagnostic methods involve the use of natural extracts of allergenic sources. Complete extracts comprise a mixture of various proteins and only 1-2% of these represent allergens. Therefore, these extracts are difficult to standardize regarding the amount of contained allergens and not designated to exactly define the disease-eliciting allergenic molecules. The only causative treatment for Type I allergy is specific immunotherapy (SIT). A conventional treatment consists of the subcutaneous injection of native allergen extract into allergic patients according to standardized protocols in order to induce specific tolerance in the allergic patient. Although SIT is an effective treatment, it has some disadvantages. First, the indication and success of SIT are strongly related with the phenotype of allergic disease, i.e. individuals allergic to various allergens have a smaller likelihood of clinical success than mono-sensitized patients. Second, SIT bears the potential risk to induce a sensitization to additional allergens contained in the complete extract which were originally not recognized by the patient. Third, the administration of allergens may trigger undesired anaphylactic reactions.
RECOMBINANT ALLERGENS
Advances in the field of molecular protein characterization have allowed the identification and production of allergens by recombinant DNA technology. Most allergens are soluble proteins or glycoproteins with a molecular weight between 5-70 kDa and can be produced in recombinant form. In contrast to native allergen extracts, recombinant allergens are pure, well-defined substances with a standardizable concentration. The use of recombinant allergens as diagnostic tools can improve the sensitivity, reliability and accuracy of the diagnostic material for serological assays and provocation tests. Employing different recombinant allergens enables the analysis of the reactivity profile of allergic individuals, i.e. whether a patient recognizes only one or more allergens. This concept was termed “component-resolved diagnosis“ (CRD). Hence, with the help of CRD the disease-causing allergens can exactly be defined for each allergic patient which is an important first step to clarify before the start of an allergy treatment. The use of recombinant allergens as vaccines for SIT might improve the efficacy and safety of this treatment. Based on CRD, only the disease-eliciting allergen(s) are administered which does not bear the risk to induce an unwanted new sensitization during a therapy. Undesired side-effects can be reduced if a well-defined single allergen or mixture of allergens is administered.
