D3.14 - IgE sensitisation to parvalbumin, Ani s 1, tropomyosin and arginine kinase delineates distinct molecular endotypes of seafood allergy

Seafood allergy is characterised by heterogeneous IgE sensitisation to distinct molecular components. Multiplex molecular diagnostics may identify clinically meaningful molecular endotypes to distinguish genuine sensitisation from cross-reactivity and improve risk stratification. This study aimed to define whether specific molecular profiles (endotypes) can predict clinical severity better than extract-based tests.

In this multicentre prospective study (January 2021–December 2025), 8040 patients were screened using a macroarray-based multiplex immunoassay. Among them, 787 subjects (9.8%) showed IgE sensitisation to at least one seafood-derived molecule from fish, crustaceans, molluscs, or Anisakis simplex. Sensitisation profiles to major panallergens and muscle-related proteins were analysed using Principal Component Analysis (PCA), unsupervised hierarchical clustering, and multivariable logistic regression. These molecular patterns were then correlated with prospectively collected clinical phenotypes classified as mild, moderate, or severe/anaphylaxis.

Tropomyosin (n = 357; 45%), arginine kinase (n = 290; 37%), parvalbumin (n = 189; 24%) and Ani s 1 (n = 94; 12%) were the most prevalent sensitisations and showed limited overlap, defining largely independent molecular endotypes. After adjustment, parvalbumin and Ani s 1 were independently associated with severe reactions (ORadj 3.7, 95% CI 2.3–6.1; and 2.7, 95% CI 1.5–4.8). Arginine kinase was predominantly associated with mild phenotypes (ORadj 5.3, 95% CI 3.4–8.4), whereas tropomyosin correlated mainly with moderate reactions. PCA and clustering revealed modular sensitisation patterns with component-specific severity associations.

Seafood allergy comprises distinct molecular endotypes associated with differential clinical risk that require tailored management. Multiplex molecular allergology enables clinically actionable and targeted risk stratification.