# Molecular allergens drive risk stratification and immunotherapy in Hymenoptera venom allergy

## TL;DR

This study shows how molecular allergen testing improves diagnosis and treatment of Hymenoptera venom allergies, helping predict severe reactions and track immunotherapy progress.

## Contribution

The study identifies specific allergens as predictors of clinical outcomes and reveals differential IgE reduction patterns during immunotherapy.

## Key findings

- Systemic reactions were more common in males, while large local reactions were more frequent in females.
- Sensitization to Vespula spp. and Polistes dominula was higher than to Apis mellifera.
- IgE to specific allergens like Api m 1 and Ves v 5 independently predicted systemic reactions.

## Abstract

Hymenoptera venom allergy is a major cause of life-threatening anaphylaxis. Molecular diagnostics have improved the characterisation of sensitisation patterns, although the clinical role of cross-reactive allergens such as DPPIV and hyaluronidases remains unclear.

To define IgE sensitisation to venom components, examine associations with clinical phenotypes, and assess the immunological impact of venom immunotherapy (VIT) in an Italian cohort.

In this monocentric study, 378 patients with documented Hymenoptera adverse reactions underwent extract-based and component-resolved diagnostics. A prospective subset (n = 113) was followed during VIT. Commercial venom extracts were characterised by inhibition assays.

Systemic reactions occurred in 36% of patients, predominantly males, while large local reactions were more common in females. Sensitisation to Vespula spp. (52%) and Polistes dominula (48%) exceeded Apis mellifera (26%). Api m 1/3/10 and Ves v 5/Pol d 5 were the most relevant allergens. Multivariate analysis identified IgE to Api m 1, Api m 3, Ves v 1, and Ves v 5 as independent predictors of systemic reactions. Mixed-effect models revealed a progressive decline of species-specific IgE during VIT, with an earlier progressive reduction of Ves v 1 and Ves v 5 and a delayed decrease of Api m 1, while IgE to panallergens remained stable.

Molecular diagnostics refine risk stratification and monitoring of VIT. Species-specific allergens provide reliable clinical markers, whereas panallergens help distinguish true double sensitisation from cross-reactivity. VIT induces a progressive but differential reduction in specific IgE and confers protection, supporting precision allergy care.