# Rapid Change in FcεRI Occupancy on Basophils After Venom Immunotherapy Induction

## TL;DR

This study examines how venom immunotherapy affects basophil receptors in allergy patients, finding rapid changes in receptor occupancy without significant serum markers.

## Contribution

The study reveals rapid FcεRI receptor changes on basophils during early venom immunotherapy, offering new insights into cellular tolerance mechanisms.

## Key findings

- VIT increased unoccupied FcεRI on basophils, especially in patients with high IgE and low baseline unoccupied FcεRI.
- Serum tryptase and sFcεRI levels remained largely unchanged after VIT induction.
- BAT results were heterogeneous, with EC50 changes correlating to FcεRI receptor density.

## Abstract

Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. To address this, total and unoccupied high-affinity IgE receptor (FcεRI) numbers per basophil, soluble FcεRI (sFcεRI) and serum tryptase levels were measured before and after the first day of VIT induction in HVA patients. Additionally, basophil activation tests (BATs) were performed at those time points. In the early phase of VIT induction, no significant change in total FcεRI receptor density on basophils was observed, but a significant increase in unoccupied FcεRI was noticeable, predominantly in patients with high total IgE and low baseline unoccupied FcεRI density. No meaningful difference in serum tryptase levels or sFcεRI levels was observed after VIT induction. BATs showed heterogeneous results, often unchanged before and after VIT (in 47% of the cases), sometimes increased (in 40%) and only rarely decreased EC50 sensitivity (in 13%). Changes in the BAT EC50 correlated with FcεRI receptor density changes in basophils. In summary, VIT induction led to an increased ratio of unoccupied-to-total FcεRI without notable tryptase or sFcεRI serum elevation, pointing towards subthreshold cell activation with receptor internalization and recycling. However, the mostly unchanged or even increased basophil sensitivity in EC50 calls for further research to clarify the clinical relevance of these rapid receptor modulations.