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Division of Immunopathology
Department of Pathophysiology and Allergy Research
Center of Pathophysiology, Infectiology & Immunology

Medical University of Vienna

Vienna General Hospital, AKH, 3Q
Waehringer Guertel 18-20
A-1090 Vienna, Austria

The nasal mucosa: a critical site for induction and maintenance, but also for prevention and therapy of Type I allergy [Niederberger]

Project summary

Allergic rhinitis is the most common manifestation of type I allergy and the nasal mucosa is an important site for contact with respiratory allergens. During the first six years of this project we have demonstrated that nasal but not dermal exposure to respiratory allergens leads to a boosting of serum IgE levels, which cannot be suppressed by treatment with intranasal corticosteroids. Elevated systemic IgE levels were associated with increased systemic sensitivity. We also have shown that immunotherapy with recombinant allergen derivatives induces blocking IgG antibodies directed at epitopes not recognized before therapy, and that blocking antibodies appear not only in the sera but also in nasal secretions of vaccinated patients where they protect against allergic inflammation and possibly against allergen-induced boosts of systemic IgE responses. Our results thus support the concept that the nose is not only an important site of allergic inflammation, but is also critically involved in the regulation of systemic allergic immune responses.
We have also investigated environmental factors influencing nasal allergen intrusion and have demonstrated that cigarette smoke damages the respiratory epithelium and may thus increase allergic inflammation. Furthermore, interferon-gamma a cytokine which appears at sites of chronic allergic inflammation, was shown to increase allergen penetration through respiratory mucosa by a receptor-mediated mechanism and hence may contribute to allergen-driven inflammation and boosts of IgE memory responses.
In the coming project period we plan to continue the analysis of factors and mechanisms that influence allergen penetration through the respiratory mucosa. In particular we are interested to study the effects of rhinovirus infections which are supposed to be connected with asthma exacerbations on allergen penetration in the nose. Furthermore, we plan to investigate whether the systemic boost of allergen-specific IgE can be elicited also by bronchial and oral allergen contact. In this context we are interested to study whether there is a difference between native-like allergens and hypoallergenic allergen derivatives with reduced or no IgE reactivity but preserved T cell epitopes on the induction of systemic allergen-specific immune response via the nasal and oral mucosa . These studies may reveal molecular mechanisms (i.e., involved epitopes) of allergen-induced boosts of systemic immune responses and may ultimately be useful to identify allergen derivatives which are particularly useful for mucosal immunotherapy. In addition we plan to characterize cells involved in the boost of systemic IgE following allergen contact by analyzing IgE producing cells in the peripheral blood and nasal mucosa. Finally, we plan to continue to analyse the IgG response induced by immunotherapy with recombinant allergens, in particular its effect on T cell responses and to compare the magnitude and quality of this response with that of established immunotherapy protocols based on crude allergen extracts. These studies should ultimately lead to the development of therapeutic strategies for allergy that target allergen contact at the nasal mucosa.