High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy

Summary: Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in s...

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Main Authors: Genghao Chen, Ellen L. Shrock, Mamie Z. Li, Jonathan M. Spergel, Kari C. Nadeau, Jacqueline A. Pongracic, Dale T. Umetsu, Rima Rachid, Andrew J. MacGinnitie, Wanda Phipatanakul, Lynda Schneider, Hans C. Oettgen, Stephen J. Elledge
Format: Article
Language:English
Published: Elsevier 2021-10-01
Series:Cell Reports Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666379121002688
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author Genghao Chen
Ellen L. Shrock
Mamie Z. Li
Jonathan M. Spergel
Kari C. Nadeau
Jacqueline A. Pongracic
Dale T. Umetsu
Rima Rachid
Andrew J. MacGinnitie
Wanda Phipatanakul
Lynda Schneider
Hans C. Oettgen
Stephen J. Elledge
author_facet Genghao Chen
Ellen L. Shrock
Mamie Z. Li
Jonathan M. Spergel
Kari C. Nadeau
Jacqueline A. Pongracic
Dale T. Umetsu
Rima Rachid
Andrew J. MacGinnitie
Wanda Phipatanakul
Lynda Schneider
Hans C. Oettgen
Stephen J. Elledge
author_sort Genghao Chen
collection DOAJ
description Summary: Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies. We observe a striking diversification and boosting of the peanut-specific IgG repertoire after OIT and a reduction in pre-existing IgE levels against individual epitopes. High-resolution epitope mapping reveals shared recognition of public epitopes in Ara h 1, 2, 3, and 7. In individual subjects, OIT-induced IgG specificities overlap extensively with IgE and exhibit strikingly similar antibody footprints, suggesting related clonal lineages or convergent evolution of peanut-specific IgE and IgG B cells. Individual differences in epitope recognition identified via AllerScan could inform safer and more effective personalized immunotherapy.
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spelling doaj.art-393b68bda2814b4c96490fe3b2cb72c02022-12-21T19:14:41ZengElsevierCell Reports Medicine2666-37912021-10-01210100410High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapyGenghao Chen0Ellen L. Shrock1Mamie Z. Li2Jonathan M. Spergel3Kari C. Nadeau4Jacqueline A. Pongracic5Dale T. Umetsu6Rima Rachid7Andrew J. MacGinnitie8Wanda Phipatanakul9Lynda Schneider10Hans C. Oettgen11Stephen J. Elledge12Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02115, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02115, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USADivision of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine of University of Pennsylvania, Philadelphia, PA, USADepartment of Medicine, Sean N Parker Center for Allergy and Asthma Research, Stanford University, Palo Alto, CA, USADivision of Pediatric Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Department of Pediatrics, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA 02115, USA; Corresponding authorSummary: Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies. We observe a striking diversification and boosting of the peanut-specific IgG repertoire after OIT and a reduction in pre-existing IgE levels against individual epitopes. High-resolution epitope mapping reveals shared recognition of public epitopes in Ara h 1, 2, 3, and 7. In individual subjects, OIT-induced IgG specificities overlap extensively with IgE and exhibit strikingly similar antibody footprints, suggesting related clonal lineages or convergent evolution of peanut-specific IgE and IgG B cells. Individual differences in epitope recognition identified via AllerScan could inform safer and more effective personalized immunotherapy.http://www.sciencedirect.com/science/article/pii/S2666379121002688peanut allergyantibodyantibody repertoirephage displayoral immunotherapyfood allergy
spellingShingle Genghao Chen
Ellen L. Shrock
Mamie Z. Li
Jonathan M. Spergel
Kari C. Nadeau
Jacqueline A. Pongracic
Dale T. Umetsu
Rima Rachid
Andrew J. MacGinnitie
Wanda Phipatanakul
Lynda Schneider
Hans C. Oettgen
Stephen J. Elledge
High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy
Cell Reports Medicine
peanut allergy
antibody
antibody repertoire
phage display
oral immunotherapy
food allergy
title High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy
title_full High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy
title_fullStr High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy
title_full_unstemmed High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy
title_short High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy
title_sort high resolution epitope mapping by allerscan reveals relationships between ige and igg repertoires during peanut oral immunotherapy
topic peanut allergy
antibody
antibody repertoire
phage display
oral immunotherapy
food allergy
url http://www.sciencedirect.com/science/article/pii/S2666379121002688
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