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Cosensitization to the 3 Nonhomologous Major Cashew Allergens Ana o 1, Ana o 2, and Ana o 3 Is Caused by IgE Cross-reactivity

Kabasser S1, Radauer C1, Eber E2, Haber ME2, Hieden K2, Zieglmayer P3,4, Kost LE5, Sindher SB5, Chinthrajah S5, Geiselhart S1, Hoffmann-Sommergruber K1, Nadeau KC5,6, Breiteneder H1, Bublin M1

1Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna,
Vienna, Austria
2Division of Pediatric Pulmonology and Allergology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
3Vienna Challenge Chamber, Allergy Center Vienna West, Vienna, Austria
4Competence Center for Allergology and Immunology, Karl Landsteiner University, Krems, Austria
5Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, USA
6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, USA

J Investig Allergol Clin Immunol 2024; Vol 34(1) : 38-48
doi: 10.18176/jiaci.0867

Background: Cashew nuts often cause strong allergic reactions, which are even more severe than those of peanuts. Ana o 1 (vicilin), Ana o 2 (legumin), and Ana o 3 (2S albumin) are major cashew allergens. Cosensitization to all 3 nonhomologous cashew nut allergens has been observed. We hypothesize that this might be due to IgE cross-reactivity.
Methods: IgE cross-inhibitions were performed with Ana o 1-3 using serum samples from cashew nut–allergic patients. The related hazelnut allergens Cor a 11, 9, and 14 were used as controls. For comparison, IgE cross-reactivity between the hazelnut allergens was investigated using serum samples from hazelnut-allergic patients.
Results: The median percentages of cross-inhibition between Ana o 1, 2, and 3 were 84%-99%. In comparison, the median cross- inhibition values between hazelnut allergens were 33%-62%. The IC50 values revealed the highest IgE affinity to be to Ana o 3 and Cor a 14. Hazelnut legumin Cor a 9 inhibited IgE binding to Ana o 1, 2, and 3, with median percentages of 75%, 56%, and 48%, respectively. No cross-reactivity was observed between allergenic vicilins or between 2S albumins from cashew and hazelnut. Potentially cross-reactive peptides of Ana o 3 identified in silico overlapped with previously reported IgE epitopes of all 3 allergens.
Conclusion: IgE with high affinity to Ana o 3 that cross-reacts with the other 2 major nonhomologous cashew nut allergens might be responsible for the high allergenic potency of cashew nut. These cross-reactive IgE types comprise the major fraction of specific IgE in cashew-allergic patients and might be responsible for cross-reactivity between unrelated tree nuts. 

Key words: Cashew nut allergy, IgE cross-reactivity, Food allergens, Food allergy, Hazelnut allergy, Hazelnut allergens, Tree nut allergy