House dust mite sensitization shapes the clinical expression of shellfish allergy

<b>Background.</b> Cross-reactivity among phylogenetically distant invertebrates-such as mites, crustaceans, and mollusks-is mainly driven by conserved panallergens including tropomyosin, arginine kinase, and troponin C. However, the clinical impact and molecular basis of these cross-reactivities remain incompletely defined. <b>Methods.</b> A multicenter observational study was conducted in 3,777 patients reactive to at least one arthropod or invertebrate allergen component. Serum IgE profiles were assessed using the ALEX²® multiplex platform, including allergens from mites, crustaceans, mollusks, and related taxa. Clinical data were analyzed according to molecular sensitization patterns. <b>Results.</b> Mite sensitization was detected in nearly 80% of patients, 80% of whom showed co-sensitization to other invertebrates. Sensitization to mollusks and/or crustaceans occurred in 31.9% (n = 1,207), with a marked predominance of concomitant mite sensitization (79.1% for crustaceans, 60.3% for mollusks). Clinically relevant shellfish reactions were reported in > 95% of patients co-sensitized to mites and shellfish allergens but were uncommon among those mono-sensitized to decapod or mollusk components. Tropomyosin-specific IgE was detected in > 95% of symptomatic individuals and was significantly associated with moderate-to-severe reactions (p < 0.001). <b>Conclusions.</b> Mite-shellfish co-sensitization defines the major molecular and clinical phenotype of shellfish allergy, supporting a model in which mite-derived tropomyosin acts as the primary sensitizer enabling cross-reactivity to homologous invertebrate proteins. In contrast, isolated shellfish sensitization rarely results in symptoms. Component-resolved diagnostics are crucial to identify at-risk patients and to avoid unnecessary dietary restrictions.