English walnuts are frequently associated with severe allergic reactions. We sought English walnut cultivars or other walnut species for which IgE binding to walnut seed storage proteins was decreased or the ability to inhibit IgE binding to English walnut extract was incomplete, thereby identifying possible germplasm sources of hypoallergenic walnut seed storage proteins.

Sera from patients who have had life-threatening systemic reactions to English walnut were used in immunoblots to identify IgE-reactive proteins in the walnut species and cultivars. In addition, the same sera were used in immunoblot inhibition with several species to determine in vitro cross-reactivity of recombinant and native Jug r 1 and Jug r 2, two important walnut allergens.

Patient IgE showed similar binding to all walnut extracts with some minor differences between the English and black walnut species. Inhibition with the various walnut species eliminated nearly all IgE binding to the proteins in both the English walnut Chandler cultivar and the Black Walnut Thomas cultivar. Absorption with all walnut species eliminated IgE binding to the recombinant Jug r 2 and decreased IgE binding to the recombinant Jug r 1.

It is unlikely a hypoallergenic walnut could be bred from available germplasm. Furthermore, based on the extensive cross-reactivity seen in vitro, patients with severe English walnut allergy will likely react to all commercial English walnut cultivars and other closely-related walnut species.