Wheat and maize thioredoxins: A novel cross-reactive cereal allergen family related to baker's asthma

Background: Baker's asthma is a serious problem for a significant proportion of workers in bakeries, confectionaries, and the food industry. Although several wheat allergens related to baker's asthma have been described, standardized reagents for a reliable diagnosis are not yet available. Objective: To clone novel wheat allergens related to baker's asthma and investigate the cross-reactive potential of their maize and human homologues. Methods: A wheat cDNA phage display library was screened with sera from bakers with occupational asthma for IgE-binding structures. Homologous sequences from maize and human thioredoxins were amplified from corresponding cDNA libraries. Results: Within the enriched wheat cDNA repertoire we identified., among others, the sequence encoding wheat thioredoxin-hB (Triticum aesthvum allergen 25 [Tri a 25]). The recombinant protein displayed enzymatic activity, and we observed a sensitization rate of 47% among bakers with occupational asthma and of 35% among patients with grass pollen allergy, but without a clinical history of cereal allergy. Furthermore, the previously characterized maize thioredoxin-h1 (Zea mays allergen 25 [Zea m 25]), sharing 74% identity with Tri a 25, exhibited distinct IgE cross-reactivity with its wheat homologue. Two bakers also showed sensitization to human thioredoxin, which shares 29% identity with Tri a 25. In a comparative study, we included recombinant alpha-amylase inhibitor 0.19, showing a sensitization rate of 65% in individuals with baker's asthma. Conclusion: Thioredoxins represent a novel family of cross-reactive allergens that might contribute to the symptoms of baker's asthma and might in addition be related to grass pollen allergy, as indicated by the reactivity of grass pollen allergic patients to cereal thioredoxins. Clinical implications: The recombinant cereal thioredoxins will, together with the already reported wheat allergens, contribute to a more reliable diagnosis of baker's asthma and, perhaps, become a tool for the development of component-resolved immunotherapy.