Unveiling regional patterns of IgE sensitization to peanut, hazelnut, and walnut in Italy: a nationwide bottom-up molecular survey

BACKGROUND: Tree nut and peanut allergy is increasing in prevalence across Europe, yet the molecular sensitization patterns underlying these allergies remain incompletely defined in Southern Europe, particularly in Italy. OBJECTIVE: To characterize regional profiles of IgE sensitization to allergenic components of peanut, hazelnut, and walnut across Italy using a bottom-up, molecule-based diagnostic approach. METHODS: multiplex platform. Co-sensitization patterns and regional variations were explored through Euler-Venn analysis. RESULTS: All patients were sensitized to at least one nut allergen, revealing distinct geographic trends. In Northeast Italy, PR-10 proteins predominated (up to 63 %), consistent with birch-related cross-reactivity. In contrast, nsLTP sensitization was highly prevalent in the South (up to 91 %), while Central Italy showed intermediate profiles. Co-sensitization to PR-10 and nsLTPs in the Northeast was not associated with milder reactions. Sensitization to seed storage proteins progressively decreased from North to South. Jug r 1 was the predominant walnut allergen in the Northeast, whereas Jug r 2 and Jug r 3 prevailed in the South. Sensitization to oleosins was rare (<2 %). CONCLUSION: Italy represents a microcosm of Europe in terms of molecular allergy endotypes, showing a clear North-South gradient in nut allergen sensitization. Multiplex molecular diagnostics unveil region-specific co-sensitizations with potential clinical relevance and support geographically tailored diagnostic and management strategies within a precision allergy framework.