The role of IgG1 and IgG4 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 IgG4; however, our recent studies indicated the dominance of IgG1 early in AIT. Objectives: Here, the IgE-blocking activity and avidity of allergen-specific IgG1 and IgG4 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 IgG1 and IgG4 levels were determined by ELISA and ImmunoCAP, respectively. Unmodified and IgG1- or IgG4-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 IgG1 and IgG4 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 IgG1 clearly diminished the inhibition of basophil activation while the absence of IgG4 hardly reduced IgE-blocking. Then, IgG4 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-IgG1 complexes were enduringly more stable than Bet v 1-IgG4 complexes were. Conclusions: In spite of the constant avidity of AIT-induced allergen-specific IgG1 and IgG4 antibodies, their dominance in IgE-blocking shifted in the course of treatment. The blocking activity of allergen-specific IgG1 should not be underestimated, particularly early in AIT. (J Allergy Clin Immunol 2023;151:1371-8.)

Automated summary

The blocking activity and avidity of allergen-specific IgG1 and IgG4 antibodies were monitored throughout 3 years of allergen immunotherapy (AIT). It was found that IgG1 dominated in the early stage of AIT, while IgG4 played an important role in IgE-blocking activity. Depletion of IgG1 significantly reduced the inhibition of basophil activation in the first year of therapy, while the absence of IgG4 hardly affected IgE-blocking.