Molecular sensitization profiles and β-parvalbumin sensitization burden associated with clinical fish allergy in children.

BACKGROUND

Fish allergy is a potentially severe condition that is frequently managed with broad elimination diets. Molecular allergology may improve risk stratification by distinguishing clinically relevant fish allergy from asymptomatic sensitization. We aimed to characterize molecular sensitization patterns in fish-sensitized children and identify molecular profiles associated with clinical fish allergy.

METHODS

Sixty-one fish-sensitized children (0-18 years) were evaluated using a multiplex molecular allergy assay (ALEX2). Twenty-eight children were classified as fish-allergic based on a positive oral food challenge (OFC) or consistent clinical reactions, whereas 33 sensitized children were clinically tolerant. Molecular sensitization patterns were analyzed using Bayesian logistic model averaging (BMA), Firth penalized logistic regression, receiver operating characteristic (ROC) analysis, and hierarchical clustering.

RESULTS

Sensitization to β-parvalbumins was significantly more frequent in allergic than tolerant children. Allergic children also exhibited a substantially higher cumulative β-parvalbumin sensitization burden (median 7 [IQR 5-7] vs 3 [IQR 1-5]; p<0.001). BMA prioritized Clu h 1, Gad m 2_3, and Cyp c 1 as the molecular allergens most strongly associated with clinical fish allergy. Sensitization to Gad m 2_3 was observed exclusively among allergic children. An exploratory parsimonious model incorporating cumulative β-parvalbumin sensitization burden together with Gad m 2_3 achieved an optimism-corrected AUC of 0.867.

CONCLUSIONS

Molecular sensitization profiles, particularly the cumulative burden of β-parvalbumin sensitization, were associated with clinical fish allergy in children. Clu h 1 and Cyp c 1 emerged as the molecular markers most consistently associated with clinical reactivity, whereas Gad m 2_3 was observed only among allergic children in this cohort and may represent a low-prevalence exploratory finding. These findings suggest a potential role for molecular allergen profiling in risk stratification among fish-sensitized children but require validation in larger independent cohorts before clinical application.