Profiling serum antibodies with a pan allergen phage library identifies key wheat allergy epitopes

• Published in: Nature communications 2021-01, Vol.12 (1), p.379-379, Article 379
• Main Authors: Monaco, Daniel R., Sie, Brandon M., Nirschl, Thomas R., Knight, Audrey C., Sampson, Hugh A., Nowak-Wegrzyn, Anna, Wood, Robert A., Hamilton, Robert G., Frischmeyer-Guerrerio, Pamela A., Larman, H. Benjamin
• Format: Article
• Language: English
• Subjects: 49; 49/1; 631/250/2152/2153/1291; 631/250/347; 631/553/794; 692/308/575; Adolescent; Adult; Allergens; Allergens - genetics; Allergens - immunology; Allergic reactions; Allergies; Antibodies; Antibodies - blood; Antibodies - immunology; Antigens; Antimicrobial Cationic Peptides - immunology; Child; Child, Preschool; Display devices; Epitopes; Epitopes - immunology; Female; Food allergies; Humanities and Social Sciences; Humans; Hypersensitivity - immunology; Immunoglobulin E; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunological tolerance; Immunotherapy; Libraries; Male; Middle Aged; multidisciplinary; Peptide Library; Phage display; Phages; Placebos; Plant Proteins - immunology; Proteins; Reactivity; Science; Science (multidisciplinary); Wheat; Wheat Hypersensitivity - immunology; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20622-1

Allergic reactions occur when IgE molecules become crosslinked by antigens such as food proteins. Here we create the ‘AllerScan’ programmable phage display system to characterize the binding specificities of anti-allergen IgG and IgE antibodies in serum against thousands of allergenic proteins from hundreds of organisms at peptide resolution. Using AllerScan, we identify robust anti-wheat IgE reactivities in wheat allergic individuals but not in wheat-sensitized individuals. Meanwhile, a key wheat epitope in alpha purothionin elicits dominant IgE responses among allergic patients, and frequent IgG responses among sensitized and non-allergic patients. A double-blind, placebo-controlled trial shows that alpha purothionin reactivity, among others, is strongly modulated by oral immunotherapy in tolerized individuals. AllerScan may thus serve as a high-throughput platform for unbiased analysis of anti-allergen antibody specificities. A diverse array of antigens can trigger allergic reactions. Here the authors present the ‘AllerScan’ programmable phage display library, which is an efficient and unbiased approach for profiling anti-allergen antibody reactivities at cohort scale, with which a key wheat epitope is found to distinguish between wheat allergy and tolerance.