Global variations of IgE cross-reactivity in Cupressus allergy.

Background: Seasonal allergic rhinitis triggered by Cupressaceae species is a significant concern worldwide, particularly in regions such as Japan, China, Spain, and the United States. Objective: This study investigated specific IgE responses to Cupressaceae species and the potential clinical relevance of cross-reactivity, focusing on Japanese cedar (Cryptomeria japonica [Cry j]), which is a major allergenic species in Japan. Methods: We analyzed serum samples from 609 patients across 4 countries to measure levels of specific IgE using ImmunoCAP. We assessed IgE reactivity against Cry j extract and other Cupressaceae species, including Arizona cypress and red cedar extracts, to delineate patterns of reactivity. Results: Levels of specific IgE against Cry j were markedly elevated in Japanese samples; they were nearly 10-fold higher than those against other allergens. In contrast, samples from China, Spain, and the United States showed lower levels of Cry j-specific IgE, with significant levels of reactivity against Cupressus arizonica and mountain cedar (Juniperus ashei) species. Inhibition assays demonstrated that Cry j extract significantly inhibited IgE binding, particularly in Japan, suggesting dominant Cry j-specific antibodies, whereas cross-inhibition was lower in other countries. Geographic differences in pan-allergen reactivity were observed, with a notable prevalence of profilin and cross-reactive carbohydrate determinant-specific IgE in samples from the United States but minimal reactivity in samples from Japan and China. Conclusion: These findings indicate notable geographic variations in specific IgE reactivity and cross-reactivity among Cupressaceae species, thus underscoring the importance of tailoring diagnostic and therapeutic approaches in allergy treatment based on region-specific allergen exposure patterns.