Today,
in vivo
allergy diagnosis and allergen-specific immunotherapy (AIT) are still based on allergen extracts obtained from natural allergen sources. Several studies analyzing the composition of natural allergen extracts have shown severe problems regarding their quality such as the presence of undefined nonallergenic materials, contaminants as well as high variabilities regarding contents and biological activity of individual allergens. Despite the increasing availability of sophisticated analytical technologies, these problems cannot be overcome because they are inherent to allergen sources and methods of extract production. For
in vitro
allergy diagnosis problems related to natural allergen extracts have been largely overcome by the implementation of recombinant allergen molecules that are defined regarding purity and biological activity. However, no such advances have been made for allergen preparations to be used
in vivo
for diagnosis and therapy. No clinical studies have been performed for allergen extracts available for
in vivo
allergy diagnosis that document safety, sensitivity, and specificity of the products. Only for very few therapeutic allergen extracts state-of-the-art clinical studies have been performed that provide evidence for safety and efficacy. In this article, we discuss problems related to the inconsistent quality of products based on natural allergen extracts and share our observations that most of the products available for
in vivo
diagnosis and AIT do not meet the international standards for medicinal products. We argue that a replacement of natural allergen extracts by defined recombinantly produced allergen molecules and/or mixtures thereof may be the only way to guarantee the supply of clinicians with state-of-the-art medicinal products for
in vivo
diagnosis and treatment of allergic patients in the future.
Background-Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% children and 9% adults worldwide. AD patients are often sensitized against a broad variety of allergens and more than 90% of them suffer from skin superinfections with Staphylococcus aureus.
Purpose of reviewMolecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis.Recent findingsIgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE- and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach.SummaryMolecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach.
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