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

João Rodrigues Grilo, Claudia Kitzmüller, Lorenz Aglas, Gabriela Sánchez Acosta, Ute Vollmann, Christof Ebner, Fritz Horak, Tamar Kinaciyan, Christian Radauer, Fatima Ferreira, Beatrice Jahn-Schmid, Barbara Bohle

Research output: Journal article (peer-reviewed)Journal article

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2555-2564
Number of pages10
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume76
Issue number8
DOIs
Publication statusPublished - Aug 2021
Externally publishedYes

Keywords

  • Allergens
  • Antibodies, Blocking
  • Antigens, Plant/immunology
  • Fagales
  • Humans
  • Immunoglobulin E
  • Plant Proteins
  • Recombinant Proteins
  • Sublingual Immunotherapy

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