Art v 1 and Amb a 4 Co‐Sensitization Identifies Italian Patients at Risk for Mugwort‐Celery‐Spice Syndrome

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BACKGROUND: Pollen defensins such as Art v 1 (mugwort) and Amb a 4 (ragweed) are pivotal allergens in pollen-food syndromes, but their clinical role in Southern Europe is poorly defined. OBJECTIVE: To characterize sensitization to defensins and related allergens in Italy and its association with clinical phenotypes. METHODS: Between 2021 and 2025, 7176 patients underwent molecular testing in three Italian centers. Sensitization to the pollen defensins Art v 1 and Amb a 4 was evaluated, together with celery allergens representing different protein families: the PR-10 Api g 1, the nsLTPs Api g 2, Api g 6, and the defensin Api g 7 (tested in a subset). Panallergens were also assessed. RESULTS: Defensin sensitization occurred in 272 patients (3.8%). Art v 1 mono-sensitization (64.7%) was largely confined to respiratory disease. Dual Art v 1-Amb a 4 sensitization (30.5%) identified a distinct subgroup at high risk of food reactions (OR = 6.9; p < 0.0001). Amb a 4 sensitization followed a clear northward gradient. Among 90 patients tested for Api g 7, 82.7% were positive, all co-sensitized to Art v 1, and one-third also to Amb a 4. IgE inhibition confirmed Art v 1 as the primary sensitizer driving defensin cross-reactivity. In contrast, Api g 2 nsLTP sensitization was strongly associated with severe systemic reactions. CONCLUSIONS: Defensin sensitization in Italy reveals distinct molecular and geographic signatures. Isolated Art v 1 sensitization dominates and marks respiratory allergy, while co-sensitization to Amb a 4-often associated with Api g 7 co-recognition-defines patients at high risk for systemic food reactions.