Enhancing Peanut and Tree Nut Allergy Diagnostics Using Linear and Conformational IgE Epitopes of Vicilin-Buried Peptides

Authors: SWIENTONIEWSKI, LAUREN - Oak Ridge Institute For Science And Education (ORISE); RAMBO, IAN - Oak Ridge Institute For Science And Education (ORISE); NESBIT, JACQUELINE - Oak Ridge Institute For Science And Education (ORISE); Cheng, Hsiaopo; GIPSON, STEPHEN - Oak Ridge Institute For Science And Education (ORISE); JONES, STACIE - University Of Arkansas; DOAN, DIEU - University Of Arkansas; DRESKIN, STEPHEN - University Of Colorado; MUSTAFA, S - University Of Rochester; SMITH, SCOTT - University Of Vanderbilt; KULIS, MICHAEL - University Of North Carolina; Rivers, Adam; FOO, ALEXANDER - National Institute Of Environmental Health Sciences (NIEHS, NIH); MUELLER, GEOFFREY - National Institute Of Environmental Health Sciences (NIEHS, NIH); Maleki, Soheila

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/20/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Peanut allergy is one of the most common food allergies and a main cause of food-induced anaphylaxis. Many with peanut allergies are also allergic to tree nuts (such as walnuts), and ways to predict what is referred to as cross-reactivity is a large concern for scientists. Reoccurring sections called leader sequences of allergenic proteins in peanut and walnut that are removed in protein processing have been shown to be types of allergens themselves. Predictions for cross-reactions by an individual to peanut and walnut have been made based on the amino acid sequences of these leader sequence sections. We have analyzed the presence of additional potential cross-reactions to amino acid sequences based on the folded structure of these sections. These findings can help predict if a peanut allergic individual may also have a reaction to walnuts or other tree nuts upon ingestion.

Technical Abstract: Rationale: Vicilin-buried peptides (VBPs) found in N-terminal vicilin leader sequences (LS) are a new class of allergens with different sequences that contribute to clinically-relevant IgE cross-reactivity due to their highly conserved structural motif called an a-hairpinin fold. We investigate and compare the IgE binding patterns to linear and conformational epitopes of peanut and walnut VBPs that have been shown to be cross-reactive. Methods: Sera IgE binding from known peanut (PN), walnut (WN), and PN+WN (PW) allergic subjects were assessed by linear peptide microarrays containing overlapping 15-mer peptides offset by 5 amino acids of Ara h 1 and Jug r 2 and by direct and competitive inhibition ELISA with VBPs from peanut (AH1.1) and walnut (JR2.1, JR2.2, JR2.3). Mixed model analysis was performed on the data to investigate linear and conformational peptide binding intensities that may have potential references for allergic status to PN, WN, or PW. ISAC data for allergens Ara h 2 and Jug r 1 was also analyzed for their potential to determine allergic status. Results: Although predicted from the linear epitopes that JR2.1 would be the immunodominant IgE target, all three intact and folded walnut VBPs competitively bound IgE at similar frequencies. We found that the IgE binding patterns and specificities for VBPs were able to distinguish between groups with WN, PN, or PW allergies. Conclusions: The comparisons in IgE binding between the predictive linear and conformational epitopes and combinations thereof are beneficial in discerning allergic status and patterns of clinically-relevant IgE cross-reactivity to peanut and tree nuts.