Zytokinexpression peripherer mononukleärer Zellen unter spezifsicher Immuntherapie bei Typ-I-Allergien der Atemwege

Die Birkenpollenallergie ist eine der meist verbreiteten Allergien in Europa. Sie zählt zu den Typ-I-Allergien, welche sich durch die Produktion allergenspezifischer Immunglobulin (Ig) E Antikörper auszeichnen, die rezeptorvermittelt an Effektorzellen der allergischen Immunantwort (eosinophile und b...

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Bibliographic Details
Main Author: Mayer, Lea
Contributors: Pfützner, Wolfgang (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2019
Online Access:PDF Full Text
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Birch pollen allergy is one of the most widespread allergies in Europe. It belongs to the type-I-allergies and is characterized by the production of allergen-specific immunoglobulin (Ig) E antibodies, which are bound by specific receptors on the surface of effector cells (eosinophilic and basophilic granulocytes, mast cells). Cross-linking of these receptors by repeated allergen contact results in cell activation with the release of proinflammatory mediators. These mediators initiate the type-I-reactions like bronchial asthma or allergic rhinitis. The specific immunotherapy (SIT) is the only causative treatment of type-I-allergies. Both the clinical effectiveness and the preventive effect were demonstrated in various clinical trials. However, the underlying immunological mechanisms are still in focus of intensive research. To detect alterations of immune parameters in peripheral blood the study was conducted with eleven patients allergic to birch pollen over the three year treatment period of SIT. In particular, main interest was on changes in cytokine levels. The closely meshed, long-term analysis enabled comparison of cytokine production at decisive time points of SIT (induction and maintenance phase) as well as in and out of birch pollen season. To evaluate the influence of natural birch pollen exposure eight subjects allergic to birch pollen treated only symptomatically and eight healthy individuals without manifestation of an IgE-mediated allergy were included in this work. Clinical efficacy was evaluated by skin prick test and by patients reporting the extent of allergic symptoms on a scale of 1 (no symptoms) to 7 (most severe symptoms). The quantitative measurement of the cytokine concentrations was performed by enzyme-linked immunosorbent assay (ELISA). Already in the first pollen season an obvious improvement of allergic symptoms was detected. During the later course of treatment, SIT resulted in a significant reduction of allergic symptoms. After one year of treatment, patients revealed decreased pricktest reactivity against birch pollen allergen. In contrast, allergic subjects only treated symptomatically did not experience a similar relief of clinical symptoms. Cellular alterations induced by SIT demonstrated strong temporal dynamics on the cytokine level. Initially, a transient increase of the immunosuppressive cytokine IL-10 was observed accompanied by parallel increases of allergy-promoting IL-5 in the first pollen season. At subsequent time points pollen induced seasonal increases of IL-5 ceased to appear, finally resulting in significantly diminished IL-5 levels at the end of the observation period. Constantly low levels of the protective cytokine interferon (IFN) γ were almost not affected by SIT. Besides a reduction at the end of the induction phase and in the third birch pollen season respectively, a slight increase was detected after the first treatment year. The common assumption that successful SIT is accompanied by a shift of a T helper (Th) 2-cell mediated to a Th1-cell dominated immune response was thus not confirmed by this study. Rather a loss of Th2 reactivity seems to be decisive. In addition, the transient increase of IL-10 release in the early phase supports a potential influence of regulatory T (Treg) cells in induction of tolerance against allergens, especially at the beginning of SIT. In summary, this study shows that tolerance induction elicited by birch pollen SIT is based on multi-factorial immune mechanisms with distinctive temporal dynamics in induction and decrease of investigated cytokines at different time points.