Microarray Analysis of Major Epitopes Among Tree Nut-Allergic Individuals May Explain Patterns of Cross-Desensitization

Rationale Oral immunotherapy (OIT) studies have demonstrated decreased sensitization to a target allergic tree nut as well as cross-desensitization with other similar tree nuts. Walnut OIT results in high rates of desensitization to pecan, yet lower rates of desensitization to other tree nuts such as hazelnut and cashew. We hypothesize that OIT driven cross-desensitization occurs more frequently between similar tree nuts due to immunoglobulin E (IgE) binding to sequentially different, yet homologous epitopes. Methods We collected serum from patients allergic to walnut, pecan, hazelnut, and/or cashew. We measured IgE binding to tree nut allergens using linear peptide microarrays. We identified the major epitopes recognized by tree nut-allergic individuals and measured their similarity to known and newly identified walnut epitopes using the Structural Database of Allergenic Proteins (SDAP). Results Common homologous and cross-reactive epitopes were identified, aligned, and compared among walnut, pecan, hazelnut, and cashew. Many walnut epitopes were recognized by pecan, hazelnut and/or cashew-allergic individuals. We identified several epitopes recognized only by hazelnut and/or cashew-allergic individuals. Conclusions Walnut epitopes recognized by pecan, hazelnut, and/or cashew-allergic individuals may underlie cross-reactions and cross-desensitization during walnut OIT. Epitopes uniquely shared among certain tree nuts, for example, those recognized by cashew or hazelnut, but not walnut or pecan-allergic individuals may be valuable for targeted multi-tree nut therapeutics. These results may also help identify those hazelnut or cashew-allergic individuals who would benefit from walnut OIT due to their recognition of walnut homologous epitopes