The role of IgG 1 and IgG 4 as dominant IgE-blocking antibodies shifts during allergen immunotherapy.

Background: The induction of allergen-specific IgE-blocking antibodies is a hallmark of allergen immunotherapy (AIT). The inhibitory bioactivity has largely been attributed to IgG ₄ ; however, our recent studies indicated the dominance of IgG ₁ early in AIT.
Objectives: Here, the IgE-blocking activity and avidity of allergen-specific IgG ₁ and IgG ₄ antibodies were monitored throughout 3 years of treatment.
Methods: Serum samples from 24 patients were collected before and regularly during AIT with birch pollen. Bet v 1-specific IgG ₁ and IgG ₄ levels were determined by ELISA and ImmunoCAP, respectively. Unmodified and IgG ₁ - or IgG ₄ -depleted samples were compared for their inhibition of Bet v 1-induced basophil activation. The stability of Bet v 1-antibody complexes was compared by ELISA and by surface plasmon resonance.
Results: Bet v 1-specific IgG ₁ and IgG ₄ levels peaked at 12 and 24 months of AIT, respectively. Serological IgE-blocking peaked at 6 months and remained high thereafter. In the first year of therapy, depletion of IgG ₁ clearly diminished the inhibition of basophil activation while the absence of IgG ₄ hardly reduced IgE-blocking. Then, IgG ₄ became the main inhibitory isotype in most individuals. Both isotypes displayed high avidity to Bet v 1 ab initio of AIT, which did not increase during treatment. Bet v 1-IgG ₁ complexes were enduringly more stable than Bet v 1-IgG ₄ complexes were.
Conclusions: In spite of the constant avidity of AIT-induced allergen-specific IgG ₁ and IgG ₄ antibodies, their dominance in IgE-blocking shifted in the course of treatment. The blocking activity of allergen-specific IgG ₁ should not be underestimated, particularly early in AIT.
(Copyright © 2023. Published by Elsevier Inc.)