Hazelnut and Walnut Vicilins in Tree Nut Allergy: Co‐Sensitization Patterns and Clinical Severity Associations
Danilo Villalta, Giulia Marcassa, Gabriella Cusa, Mariaelisabetta Conte, Francesca Buzzulini, Bo Pontoppidan, Elisabetta Caprini, Jonas Östling, Lars Mattsson, Marie Holmqvist, Mauro Giani, Lorenzo Cecchi, Riccardo Asero, Jonas Lidholm, Enrico ScalaABSTRACT
Background
Hazelnut and walnut allergy may cause severe reactions, but the clinical relevance of individual seed storage proteins, including recently available vicilins, remains incompletely defined.
Methods
We performed an observational analysis of a consecutive tertiary‐care cohort of 114 patients with tree nut allergy, including 70 with walnut allergy and 44 with hazelnut allergy. Clinical severity was classified as mild, moderate, or severe. Specific IgE to selected hazelnut and walnut components was assessed by ImmunoCAP. We evaluated sensitisation frequencies, severity‐stratified molecular profiles, and the diagnostic contribution of newly available vicilins in a singleplex format, vicilin co‐sensitisation patterns by network and heatmap analyses, ROC performance for severe reactions, and parsimonious multivariable logistic regression models adjusted for age and sex.
Results
Severe reactions were more frequent in hazelnut than in walnut allergy (43.2% vs. 24.3%). Cor a 14, Cor a 9, and Cor a 16 showed the clearest severity‐related gradients in hazelnut allergy, and Jug r 1 and Jug r 2 in walnut allergy. Co‐sensitisation was strongest between the type 2 vicilins Cor a 16 and Jug r 2. Cor a 16 showed the highest AUC among hazelnut components (0.72), with overlapping performance for Cor a 14 and Cor a 9, whereas Jug r 1 performed best among walnut components (AUC 0.89). After adjustment for age and sex, severe reactions remained associated with Cor a 14, Jug r 1, and Jug r 2.
Conclusions
In this tertiary‐care cohort, individual seed storage proteins differed in their associations with reaction severity. Cor a 14 and Jug r 1 showed the strongest adjusted associations, while type 2 vicilins dominated co‐sensitisation patterns. Overall, these findings support the clinical value of molecule‐resolved diagnostics and suggest that integrating multiple vicilin components may improve molecular stratification of tree nut allergy, although external validation is required.