Zelluläre Mechanismen der Toleranzinduktion bei der spezifischen Immuntherapie mit Allergoiden

Allergische Erkrankungen haben in den letzten Jahren in Industrie- sowie Entwicklungsländern kontinuierlich zugenommen. Die aktuellen Behandlungsmöglichkeiten beschränken sich hauptsächlich auf symptomatische Therapieverfahren. Die einzige kurative Therapieform ist derzeit die spezifische Immunt...

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Bibliographic Details
Main Author: Adams, Britta
Contributors: Bauer, Stefan (Prof. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2013
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Table of Contents: There is a continuous increase of allergic diseases in industrial countries as well as in developing countries. While most available therapies are constricted to symptomatic treatments, only the specific immunotherapy (SIT) can be considered as curative. Different forms of allergens and modes of application are utilized. Allergoids are modified types of allergens. They should be characterized by a reduced allergenicity and received immunogenicity. Thereby a saver and faster escalation of the application rate in comparison to natural allergens should be possible. Although fundamental research has progressed in the past decades elucidating the development of allergic diseases, the definite mechanism of how SIT induces immuntolerance is still a focus of intensive research. The aim of this study was the exploration of immune alterations during the firstyear SIT with an allergoid (Depigoid®) in birch-pollen allergic persons. Seven patients with birch-pollen allergy were included in this study. The clinical efficiency of SIT was evaluated by different questionnaires and skin tests. Allergen-specific IgE, total IgE and allergen-specific IgG4 was detected by ImmunoCap. In addidtion changes of the quantity of Bet v 1- (major-allergen of birch) specific Th1-, Th2- and Tr1-cells were detected by ELISPOT assay after allergenspecific-stimulation. Furthermore CD4+CD25+CD127low Treg were quantified by cytometric measurement and the proliferation of PBMC after stimulation with Bet v 1 measured. While patients showed an improvement of their medical condition, there were only marginal immunologic changes detected. Immunglobulin measurements showed only a trend of decrease for allergenspecific IgE antibodies, but almost constant data for total IgE and allergen-specific IgG4. Counts for Bet v 1- specific cells showed an increase in the first month of therapy and at the end of the first therapy year. In contrast, a decrease of Th1-cells and consequently an increase of Th2/Th1-quotient could be detected. Tr1-measurements showed an increase of Tr1-cells, but no changes of the fraction of CD4+CD25+CD127low- Treg. In summary the present study suggest that in comparison to the results of SITstudies with native allergens different immune mechanisms are responsible for tolerance induction through SIT with allergoid. Further studies with a greater number of subjects should help to elucidate these mechanisms in more detail.