Mapping antibody profiles of Bet v 1 and associated food allergens during SIT

Allergen-specific immunotherapy (SIT) represents the only curative approach for an effective and long-lasting treatment of allergic diseases. The mechanisms of SIT are well-understood and numerous immunologic parameters, which are modified during the treatment, have been identified. Nevertheless, no serologic or cellular marker is available, which can be used to determine the clinical efficacy of SIT. At the B-cell level SIT causes an initial boost of allergen-specific IgE titers followed by a decline at a later stage of the treatment. This is usually accompanied by the rise of allergen-specific IgG antibodies, at which especially IgG4 levels increase significantly. The induction of these so called blocking antibodies comprises a cardinal feature of SIT; still, IgG4 levels cannot be directly correlated with the clinical efficacy of the treatment. Consequently, determining antibody titers is insufficient to evaluate the clinical progress of SIT. Thus, we propose to investigate the humoral immune response of birch pollen allergic individuals sensitized to Bet v 1 during immunotherapy and map IgE as well as IgG antibody epitopes. Moreover, Bet v 1-mediated birch pollen allergies are frequently associated with adverse reactions towards apple Mal d 1 and hazelnut Cor a 1 described as pollen food syndrome (PFS). To date, the exact IgE specificities which elicit PFS are unknown; however, particular regions of Bet v 1 could be associated with cross-reactive IgE epitopes. In general, elevated Bet v 1-specific IgE levels seem to correlate with allergies towards Bet v 1-related food allergens. Since food allergies cannot be treated with SIT it is debated whether pollen SIT could ameliorate adverse reactions towards related food allergens. Therefore, we propose to analyse antibody profiles of patients treated with birch pollen SIT on concomitant food allergens. Bet v 1-specific antibodies (IgE, IgG1, IgG4) will be isolated from patients sera before start of treatment, after reaching the maintenance dose, and after one year of birch pollen SIT. Using NMR (nuclear magnetic resonance) spectroscopy antibody epitope mapping will be performed on Bet v 1, Mal d 1, and Cor a 1. The data will not only provide evidence about molecular mechanisms of Bet v 1-associatd PFS but allow a deep insight in the concept of blocking antibodies on allergens. This will enable us to generate more effective allergen derivatives for clinical applications in the future. Moreover, understanding the antibody pattern of Bet v 1 allergic individuals and the changes of these patterns during SIT will allow us to define predictive markers for an objective evaluation of the clinical efficacy of the treatment. Such markers will further be useful to identify non-responders prior to treatment a clear benefit for patients and clinicians.