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

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.