The role of IgG1 and IgG4 as dominant IgE-blocking antibodies shifts during allergen immunotherapy - 04/05/23
Abstract |
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.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key words : Allergen immunotherapy, antibodies, IgE-blocking, IgG4, IgG1, avidity, birch pollen, Bet v 1
Abbreviations used : AIT, BP-SCIT, PBS-T, RUs, SCIT, SPR
Mappa
| This study was supported by the Austrian Science Fund (FWF), projects P32953 and I4437, the Austrian Jubiläumsfonds, project ÖNB17947, and by the Danube Allergy Research Cluster, Country of Lower Austria, and Medical University of Vienna, Austria. |
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| Disclosure of potential conflict of interest: B. Bohle reports grants from Austrian Science Funds, Austrian Jubiläumsfonds, the Danube Allergy Research Cluster, and Medical University of Vienna, during the conduct of the study and personal fees from AllergenOnline outside the submitted work. A. Drescher is employed by Cytiva Europe GmbH, Freiburg, Germany. W. Pfützner received research support from Phadia/Thermo Fisher and honoraria as a speaker from ALK-Abelló. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 151 - N° 5
P. 1371 - Maggio 2023 Ritorno al numero
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