Phase II multicenter clinical trial of hypoallergenic 1BS-18 Hokushin bread oral immunotherapy for wheat-dependent exercise-induced anaphylaxis.

Background: Therapies for desensitizing wheat-dependent exercise-induced anaphylaxis (WDEIA), a severe allergic response to wheat ingestion and exercise, remain unestablished. This study aimed to investigate whether continuous ingestion of hypoallergenic 1BS-18 Hokushin bread, which lacks the Gli-B1 locus encoding the ω5-gliadin allergen, could achieve desensitization in adult patients with WDEIA sensitized to ω5-gliadin.

Methods: Sixteen adult patients diagnosed with WDEIA participated in this study. Each patient was administered a safety dose of bread made from 1BS-18 Hokushin wheat, a hypoallergenic wheat that defects the Gli-B1 locus responsible for encoding the ω5-gliadin allergen, over a 12-week period. The safe dose for each individual was determined through a stepwise increase in bread intake and monitored to prevent allergic reactions. Desensitization efficacy was evaluated by measuring basophil activation rates and serum allergen-specific IgE levels specific to wheat proteins using the basophil activation test and ImmunoCAP serum testing.

Results: Fourteen of the 16 patients (87.5%) successfully completed the 12-week regimen of 1BS-18 Hokushin bread, with 2 patients (12.5%) discontinuing due to allergic reactions associated with the bread. Evaluation of basophil activation rates and serum allergen-specific IgE levels indicated no significant desensitization effects in any patient.

Conclusions: Approximately 80% of patients with WDEIA were able to safely consume 1BS-18 Hokushin bread at least up to 60 g per day for 12 weeks without severe adverse reactions. However, this regimen did not achieve desensitization, suggesting that further studies may be necessary to explore alternative dosing, duration, or combinations with adjunct therapies for effective desensitization in patients with WDEIA.