The role of IgG₁ and IgG₄ as dominant IgE-blocking antibodies shifts during allergen immunotherapy.

Abstract

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. Here, the IgE-blocking activity and avidity of allergen-specific IgG₁ and IgG₄ antibodies were monitored throughout 3 years of treatment. 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. 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. 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.