# IgE to cyclophilin Bet v 7 triggers mast cell activation and mediates cross‐reactivity with Ara h 18 in children with seasonal allergic rhinitis

## TL;DR

This study shows that the cyclophilin Bet v 7 can activate mast cells and cause allergic reactions in children with seasonal allergic rhinitis, suggesting it is a clinically relevant panallergen.

## Contribution

The study demonstrates that Bet v 7 is a functional panallergen and identifies its cross-reactivity with Ara h 18.

## Key findings

- Bet v 7 activates mast cells in a dose-dependent manner and remains active after mild heat and saliva digestion.
- There is a strong correlation between IgE levels to Bet v 7 and Ara h 18.
- Bet v 7 exhibits high similarity to cyclophilins from other plant sources and similar IgE-binding properties to Ara h 18.

## Abstract

Panallergens are ubiquitously expressed molecules that may drive IgE sensitization across diverse allergen sources, thereby shaping complex clinical phenotypes such as asthma and pollen–food allergy syndrome (PFAS). Although several panallergen families have been extensively characterized, unexplained sensitization patterns are still observed in clinical practice. Cyclophilins, a conserved protein family, have recently been proposed as candidate panallergens; however, their molecular, clinical, and functional roles remain largely undefined.

Within the Panallergens in Pediatrics (PAN‐PED) cohort, we investigated 100 Italian children with seasonal allergic rhinitis (SAR) for IgE sensitization to the cyclophilins Bet v 7 and Ara h 18. Functional assays were performed by sensitizing mast cells with patient sera (n = 11) and assessing activation upon stimulation with increasing concentrations of recombinant Bet v 7 (rBet v 7), using CD63 expression as readout. Additional experiments evaluated the impact of heat treatment (60°C, 80°C, or 100°C) and saliva digestion on rBet v 7 activity.

rBet v 7 induced mast cell activation in a dose‐dependent manner, with peak responses at intermediate allergen concentrations, followed by attenuation at higher doses. rBet v 7 maintained functional activity after exposure to mild heat and saliva. A strong correlation was found between specific IgE levels to Bet v 7 and Ara h 18 (r = 0.996, p < 0.0001).

Bet v 7 has the functional capacity to activate mast cells and is resistant to mild heat and saliva digestion, supporting its role as a clinically relevant panallergen. In addition, Bet v 7 shows high similarity to cyclophilins from other plant sources and exhibits virtually identical IgE‐binding properties to Ara h 18. These findings suggest a potential rationale for considering the inclusion of cyclophilins into molecular diagnostic panels, particularly in children with SAR.