Seafood allergy comprises IgE-defined molecular sensitization endotypes associated with distinct clinical severity profiles.
6 affiliations
- 1Fondazione Luigi Maria Monti, IDI-IRCCS, Rome, Italy.
- 2U.O.C of Clinical Pathology, Buccheri La Ferla Hospital, Palermo, Italy.
- 3SC Medicina - Immunologia e Allergologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- 4Allergy and Clinical Immunology Unit, San Giovanni di Dio Hospital, Florence, Italy.
- 5S.C. di Immunologia e Allergologia di Laboratorio, PO S. Maria degli Angeli, Pordenone, Italy.
- 6Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Milan, Italy.
Abstract
Seafood allergy is characterized by heterogeneous IgE sensitization to distinct molecular components, but the clinical relevance of these profiles remains incompletely defined. Multiplex molecular diagnostics may help identify molecular endotypes and refine risk stratification. This study aimed to characterize IgE-defined molecular sensitization patterns to major seafood allergens and assess their associations with clinical reaction severity. In this multicenter prospective study (January 2021 to December 2025), 8,040 consecutive patients screened with the ALEX2 multiplex immunoassay were evaluated; 787 (9.8%) were sensitized to ≥1 seafood-derived molecule. Sensitization to parvalbumin, tropomyosin, Ani s 1, arginine kinase, and other muscle-related proteins was analyzed in relation to prospectively collected clinical phenotypes (mild, moderate, and severe). Venn analysis, principal component analysis, and unsupervised hierarchical clustering explored molecular patterns. Multivariable binary logistic regression models were fitted for each severity category versus all others, adjusting for age and sex. Associations are reported as odds ratios (ORs) with 95% CIs. Tropomyosin (45%), arginine kinase (37%), parvalbumin (24%), and Ani s 1 (12%) were the most prevalent sensitizations and showed limited overlap, delineating largely distinct molecular profiles. Hierarchical clustering and 3-dimensional principal component analysis confirmed the separation of major components in multivariate space, with distinct loading patterns. In adjusted analyses, parvalbumin (adjusted odds ratio [OR_adj], 3.7) and Ani s 1 (OR_adj, 2.7) were associated with severe reactions, tropomyosin with moderate reactions (OR_adj, 2.0), and arginine kinase with mild phenotypes (OR_adj, 5.3). Major seafood allergens define largely distinct and minimally overlapping sensitization patterns that are statistically associated with specific clinical phenotypes.
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BibTeX
@article{scala2026seafood,
title = {{Seafood allergy comprises IgE-defined molecular sensitization endotypes associated with distinct clinical severity profiles.}},
author = {Enrico Scala and Damiano Abeni and Elisabetta Caprini and Ignazio Brusca and Maria Barrale and Valerio Pravettoni and Chiara Casale and Mauro Giani and Lorenzo Cecchi and Danilo Villalta and Riccardo Asero},
journal = {The journal of allergy and clinical immunology. Global},
year = {2026},
month = sep,
doi = {10.1016/j.jacig.2026.100787},
url = {https://europepmc.org/article/MED/42999875},
note = {CC BY},
}
RIS
TY - JOUR
TI - Seafood allergy comprises IgE-defined molecular sensitization endotypes associated with distinct clinical severity profiles.
AU - Enrico Scala
AU - Damiano Abeni
AU - Elisabetta Caprini
AU - Ignazio Brusca
AU - Maria Barrale
AU - Valerio Pravettoni
AU - Chiara Casale
AU - Mauro Giani
AU - Lorenzo Cecchi
AU - Danilo Villalta
AU - Riccardo Asero
PY - 2026
DA - 2026/09/21
JO - The journal of allergy and clinical immunology. Global
DO - 10.1016/j.jacig.2026.100787
UR - https://europepmc.org/article/MED/42999875
AB - Seafood allergy is characterized by heterogeneous IgE sensitization to distinct molecular components, but the clinical relevance of these profiles remains incompletely defined. Multiplex molecular diagnostics may help identify molecular endotypes and refine risk stratification. This study aimed to characterize IgE-defined molecular sensitization patterns to major seafood allergens and assess their associations with clinical reaction severity. In this multicenter prospective study (January 2021 to December 2025), 8,040 consecutive patients screened with the ALEX2 multiplex immunoassay were evaluated; 787 (9.8%) were sensitized to ≥1 seafood-derived molecule. Sensitization to parvalbumin, tropomyosin, Ani s 1, arginine kinase, and other muscle-related proteins was analyzed in relation to prospectively collected clinical phenotypes (mild, moderate, and severe). Venn analysis, principal component analysis, and unsupervised hierarchical clustering explored molecular patterns. Multivariable binary logistic regression models were fitted for each severity category versus all others, adjusting for age and sex. Associations are reported as odds ratios (ORs) with 95% CIs. Tropomyosin (45%), arginine kinase (37%), parvalbumin (24%), and Ani s 1 (12%) were the most prevalent sensitizations and showed limited overlap, delineating largely distinct molecular profiles. Hierarchical clustering and 3-dimensional principal component analysis confirmed the separation of major components in multivariate space, with distinct loading patterns. In adjusted analyses, parvalbumin (adjusted odds ratio [OR_adj], 3.7) and Ani s 1 (OR_adj, 2.7) were associated with severe reactions, tropomyosin with moderate reactions (OR_adj, 2.0), and arginine kinase with mild phenotypes (OR_adj, 5.3). Major seafood allergens define largely distinct and minimally overlapping sensitization patterns that are statistically associated with specific clinical phenotypes.
SN - 2772-8293
ER -