IgG receptors on human basophils: Functional characterisation and significance in speicific allergen vaccination.
A collaboration between ALK Abello A/S, Michael Spangfort and H:S Rigshospitalet, Klaus Bendtzen
The incidence of allergic diseases in most western countries is increasing. Today specific allergy vaccination is the only treatment with a potential curative effect on allergic diseases. Thus, the treatment not only reduces the clinical symptoms during the treatment, but a long lasting effect on the clinical symptoms is found years after ending the treatment.
Despite the extensive clinical experience with specific allergy vaccination, the mechanisms behind the beneficial effects of the treatment are not clear. It is known, that specific allergy vaccination changes the response of the patients allergen specific T-cells towards a Th1 type response. Specific allergen vaccination also induces the production of IgG antibodies and these may act as blocking antibodies preventing allergens from binding to IgE-antibodies. Recently it has been reported that allergen specific IgG antibodies also may inhibit IgE-mediated signalling in basophils and mast cells by binding to IgG receptors of the IIb type (FcgRIIb) on these cells.
The aim of this project is to study how allergen specific IgG antibodies can inhibit IgE mediated activation of effector cells in allergic patients before, under and after specific allergen vaccination. IgG receptors on basophils from controls and allergic patients will be characterised and it will be investigated whether the expression of these is regulated by Th1/Th2 cytokines.
So far the inhibitory effect of FcgRIIb has only been demonstrated in a highly artificial system. The aim of this project is to test if an inhibitory effect of FcgRIIb signalling on IgE mediated signalling can be found in a clinically relevant allergen-system using basophils and IgE/IgG antibodies obtained from allergic patients before, under and after specific allergy vaccination.
This project involves basic research of great importance for the understanding of the regulation of allergic reactions, and for the development of new vaccines. Future allergy vaccinations will employ new ways of administration and adjuvants. Thus it is essential to know whether the induction of allergen specific IgG antibodies is necessary for a maximal effect of the treatment.
PhD student:
Cand. scient Anne Margrethe Ejrnæs Sprinkel
ALK Abelló A/S
Bøge Allé 6-8
P.O.Box 408
2970 Hørsholm
AEJ@dk.alk-abello.com