IgE‐cross‐blocking antibodies to Fagales following sublingual immunotherapy with recombinant Bet v 1

Background Evidence has accumulated that birch pollen immunotherapy reduces rhinoconjunctivitis to pollen of birch homologous trees. Therapeutic efficacy has been associated with IgE‐blocking IgG antibodies. We have recently shown that sera collected after 16 weeks of sublingual immunotherapy with recombinant Bet v 1 (rBet v 1‐SLIT) display strong IgE‐blocking bioactivity for Bet v 1. Here, we assessed whether rBet v 1‐SLIT‐induced IgG antibodies display cross‐blocking activity to related allergens in Fagales pollen. Methods IgE, IgG1 and IgG4 reactivity to recombinant Bet v 1, Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1 and Que a 1 were assessed in pre‐ and post‐SLIT samples of 17 individuals by ELISA. A basophil inhibition assay using stripped basophils re‐sensitized with a serum pool containing high Bet v 1‐specific IgE levels was established and used to assess CD63 expression in response to allergens after incubation with pre‐SLIT or post‐SLIT samples. IgG1 and IgG4 were depleted from post‐SLIT samples to assess its contribution to IgE‐cross‐blocking. Results Sublingual immunotherapy with recombinant Bet v 1 boosted cross‐reactive IgE antibodies and induced IgG1 and IgG4 antibodies with inter‐ and intra‐individually differing reactivity to the homologs. Highly variable cross‐blocking activities of post‐SLIT samples to the different allergens were found. IgG1 and IgG4 antibodies displayed cross‐blocking activity with individual variance. Conclusions Our mechanistic approach suggested that immunotherapy with the reference allergen Bet v 1 induces individual repertoires of cross‐reactive IgG1 and IgG4 antibodies. The cross‐blocking bioactivity of these antibodies was also highly variable and neither predictable from protein homology nor IgE‐cross‐reactivity. Bet v 1‐allergic individuals show IgE cross‐reactivity with allergens from Fagales. Sublingual immunotherapy with the reference allergen Bet v 1 induces individually diverse repertoires of cross‐reactive IgG1 and IgG4 antibodies. The cross‐blocking bioactivity of IgG1 and IgG4 antibodies is highly variable and not predictable from IgE‐cross‐reactivity.