Fish isoallergens and variants: database compilation,

Introduction: Fish is a major food allergy trigger with a complex variety of allergenic protein isoforms and vast species diversity exhibiting variable allergenicity. This is the first study to systematically compile fish isoallergen and variant entries associated with ingestion-related allergic reactions. Methods: Entries were compiled from four major allergen databases: World Health Organization and International Union of Immunological Societies (WHO/IUIS), AllergenOnline, Comprehensive Protein Allergen Resource (COMPARE), and Allergome, including evidence from Results: A comprehensive dataset of 79 unique fish isoallergen and variant entries from 34 fish species was identified, with 25 entries common across all four databases. AllerCatPro 2.0 achieved the highest sensitivity (97.5%). A phylogenetic tree was constructed, integrating epitope data to optimize protein family-specific thresholds for differentiating allergenic from less/non-allergenic parvalbumins. A threshold of ≥4 IEDB-mapped epitopes allowing up to two mismatches captured 52 out of 54 parvalbumin sequences (96%) in the dataset, effectively distinguishing between parvalbumin classes. Discussion: This study enhances understanding of fish allergy by systematically compiling fish isoallergens and variants and integrating B-cell epitope data. The optimized thresholds improve the performance of allergenicity prediction tools and can be applied to other protein families in future studies.