Kinetics, cross‐reactivity, and specificity of B et v 1‐specific I g G 4 antibodies induced by immunotherapy with birch pollen

Background IgE antibodies specific for the major birch pollen allergen frequently cross‐react with B et v 1 homologous food proteins, for example C or a 1 in hazelnut and Mal d 1 in apple. Specific immunotherapy with birch pollen ( BP ‐ SIT ) induces I g G 4 antibodies that inhibit I g E binding to B et v 1. However, information on cross‐reactivity of BP ‐ SIT ‐induced B et v 1‐specific I g G 4 antibodies with food allergens is limited. In this study, we investigated the kinetics of production, cross‐reactivity, and I g E ‐blocking activity of B et v 1‐specific I g G 4 antibodies emerging during conventional BP ‐ SIT and whether I g G 4‐epitopes overlapped with IgE epitopes. Methods IgE and I g G 4 levels specific for B et v 1, M al d 1, and C or a 1 were determined in 42 birch pollen–allergic patients before and during BP ‐ SIT . Inhibition of I g E binding was studied by I g E ‐facilitated antigen‐binding assays and basophil activation tests. Furthermore, inhibition of I g E ‐mediated activation of food allergen‐reactive B et v 1‐specific T ‐cell lines was assessed. Competitive immunoscreening of phage‐displayed peptides was applied to select mimotopes recognized by I g E and I g G 4 antibodies, respectively. The resulting mimotopes were mapped on the surface of the 3 D structure of the allergens using a computer‐based algorithm. Results BP‐ SIT significantly increased B et v 1‐ and food allergen‐reactive I g G 4 antibodies. In parallel, allergen‐specific I g E levels decreased significantly. Sera containing food allergen‐reactive I g G 4 antibodies inhibited I g E binding, basophil activation, and I g E ‐mediated food allergen‐induced T ‐cell proliferation. Predicted I g E and I g G 4 epitopes on all allergens showed high overlap. Conclusion Our results indicate that BP ‐ SIT may induce B et v 1‐specific I g G 4 antibodies that cross‐react with related food allergens and inhibit I g E binding by epitope competition.