Forschungszentrum Borstel
Forschungszentrum Borstel

Priority Research Area Asthma and Allergy

Clinical and Molecular Allergology

Allergy Research: General Introduction

Allergies are complex multi-organ diseases. In Germany approximately 20-30 millions of people are affected, and the prevalence is still increasing. Therefore, allergies nowadays are a widespread disease. Some allergies are life-threatening and/or pave the way for chronic diseases such as bronchial asthma as a sequel of a pre-existing allergic rhinitis (e.g. hay fever). These respiratory diseases are recurrent (like rhinitis), are prone to become a chronic illness, and affect the quality of life and overall activity. As a consequence, they lead to major socio-economic burden (Weißbuch Allergologie in Deutschland 2010).

Allergy is an immune reaction to substances of natural origin (from the natural environment) that are as such harmless. Allergies are partly driven by both, a genetic predisposition and environmental factors.

The Research Group Clinical and Molecular Allergology investigates the influence of allergen structure on sensitization/sensitization routes and on the grade of symptom severity as well as on localization (lung, gastrointestinal tract, etc.) of allergic symptoms (Molecular Phenotyping).

Projects of the RG Clinical and Molecular Allergology

1. Identification and Characterization of Novel Allergens

The identification of new allergens is a main focus of our research and shall lead to the establishment of biomarkers for clinical diagnostics and organ manifestation. Characterization of proteins in terms of structure, molecular weight, hydrophilic/lipophilic characteristics, function (e.g. protease activity) and binding to IgE from patients’ sera shall help to answer the question: What makes an allergen an allergen?
So far, the Research Group (RG) identified and isolated single allergens from plant sources which serve as marker allergens and seem to be associated with the severity of allergic symptoms. The identified allergens are: Cor a 8 (lipid transfer protein of hazelnut), Ara h 6 (storage protein of peanut), Ara h 9 (lipid transfer protein of peanut) as well as in 2015, Ara h 12 and Ara h 13 (peanut defensins) and Ara h 14 and Ara h 15 (peanut oleosins).
The determination of the interactions of allergens with the immune system and the induction of a pro-allergic immune response with resulting IgE antibody synthesis is achieved by partly cell-based structure-function analysis.

2. Investigation of Sensitization Routes

Sensitization mechanisms of certain allergens and the development of allergic diseases associated with the commonly known symptoms are rarely investigated and not fully understood. In our hands, peanut allergy serves as a model disease for allergy research: Peanut allergy affects several organ systems including the respiratory tract. It is one of the most severe allergic diseases and can sometimes be fatal. Several single peanut allergens have been identified and isolated in the RG over the years.
Some peanut allergens are very stable molecules and can be transferred via air directly inducing bronchospasm after opening a bag with peanut snack. These single allergens shall now be used as tools to elucidate sensitization and elicitation mechanisms of allergy and asthma in projects funded by the German Center for Lung Research (DZL).
In terms of food allergies, in principle sensitization can occur at the interfaces such as a) the gastrointestinal tract (orally, also via breast feeding), b) the respiratory tract, c) the skin or even earlier d) in utero before birth. One of the main questions of allergology is if peanut exposure during breast feeding may act as a sensitization route or a vector that leads to tolerance induction to peanuts very early in life. Thus, one of our research topics is the investigation on the transfer of peanut allergens into breast milk.

3. Determination of Disease Development Mechanisms

For the determination of the pathomechanism of immediate-type (type I) allergy it is crucial to elucidate how the individual production of allergy-mediating IgE antibodies is triggered by single allergens. Therefore, the specific interaction of allergens at interfaces (surface epithelium at the respiratory and gastrointestinal tract) is examined. Our aim is to elucidate how allergens are processed and metabolized and if differences exist between allergic and non-allergic individuals. Moreover, we are examining potential disturbances during immune regulation which lead to sensitization and consequently to the clinically relevant allergic reaction. Determination of allergy pathomechanisms is the rational way to battle against allergic diseases.

4. Identification and Characterization of Biomarkers for Diagnosis and Therapy

The identification of biomarkers in sera of allergic patients is another important field of research of our group. These biomarkers are, for example, a) metabolized and/or immunologically altered allergens, b) allergen-coupled carrier molecules, c) antibodies of the IgE isotype, but also d) other antibody isotypes like allergen-specific IgG and IgA, which may have anti-allergic effects. Here, certain IgE-binding motifs may serve as risk factors for the severity of clinical allergy symptoms. Also a certain allergen-specific IgE-antibody pattern (sensitization profile) may present a risk factor, e.g. a peanut-allergic patient with IgE against the storage proteins Ara h 1, 2 and 3 (see figure, panel 4).
Determination of IgE antibodies against single allergens is a molecule-specific diagnosis, and its significance is strongly dependent on the allergen source and the clinical characterization of the single allergens. This is only possible due to the close connection of the Research Group to the Allergy Outpatient Clinic at the Medical Clinic Borstel as well as the Interdisciplinary Allergy Outpatient Clinic at the University Hospital Schleswig-Holstein (UKSH), University of Lübeck (UzL), both headed by Prof. Dr. med. Uta Jappe.
The identification and characterization of clinically relevant single allergens, cloning and production of recombinant allergens as well as synthesis of peptides which are part of IgE epitopes puts us in the position to perform component-resolved diagnostics. This way, IgE antibodies specific for an allergenic protein or a certain sequential epitope can be identified and analyzed. Thus, individual sensitization patterns (“allergograms”) against different a) proteins, e.g. food allergens like peanut and lupine, house dust mite allergens, pollen, drugs like novel biological drugs, b) homologous (structurally related) proteins in different food and c) different antibody-binding motifs (IgE binding regions) of a single allergen are determined.

5. Setup of Registries and Data Bases

Data which was acquired in registries and data bases is used for epidemiologic studies and serves as a tool for the detection of new allergies. Furthermore, the Research Group is involved in the setup of the infrastructure for and participates in biomaterial collection “BioMaterialBank (BMB) Nord”.

Joint/Consortia/Cooperative Projects