HLA alleles and sustained peanut consumption promote IgG4 responses in subjects protected from peanut allergy

We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted intervention in the LEAP clinical trial. We identified an association between peanut-specific IgG4 and HLA-DQA1*01:02 that was only observed...

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Published inThe Journal of clinical investigation Vol. 132; no. 1
Main Authors Kanchan, Kanika, Grinek, Stepan, Bahnson, Henry T., Ruczinski, Ingo, Shankar, Gautam, Larson, David, Du Toit, George, Barnes, Kathleen C., Sampson, Hugh A., Suarez-Farinas, Mayte, Lack, Gideon, Nepom, Gerald T., Cerosaletti, Karen, Mathias, Rasika A.
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 01.01.2022
Subjects
2S Albumins, Plant - immunology
Alleles
Allelomorphism
Antibody Formation - genetics
Antibody Formation - immunology
Antigens, Plant - immunology
Arachis
Child
Female
Genetic aspects
Genetics
Health aspects
Histocompatibility antigens
HLA histocompatibility antigens
HLA-DQ alpha-Chains - genetics
HLA-DQ alpha-Chains - immunology
Humans
Immune response
Immunoglobulin G
Immunoglobulin G - immunology
Immunology
Male
Peanut allergy
Peanut Hypersensitivity - genetics
Peanut Hypersensitivity - immunology
Prevention
United States
MHC class 1
Genetics
Immunology
MHC class 2
Genetic variation
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Abstract We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted intervention in the LEAP clinical trial. We identified an association between peanut-specific IgG4 and HLA-DQA1*01:02 that was only observed in the presence of sustained oral peanut protein exposure. The association between IgG4 and HLA-DQA1*01:02 was driven by IgG4 specific for the Ara h 2 component. Once peanut consumption ceased, the association between IgG4-specific Ara h 2 and HLA-DQA1*01:02 was attenuated. The association was validated by observing expanded IgG4-specific epitopes in people who carried HLA-DQA1*01:02. Notably, we confirmed the previously reported associations with HLA-DQA1*01:02 and peanut allergy risk in the absence of oral peanut protein exposure. Interaction between HLA and presence or absence of exposure to peanut in an allergen- and epitope-specific manner implicates a mechanism of antigen recognition that is fundamental to driving immune responses related to allergy risk or protection.
AbstractList We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted intervention in the LEAP clinical trial. We identified an association between peanut-specific IgG4 and HLA-DQA1*01:02 that was only observed in the presence of sustained oral peanut protein exposure. The association between IgG4 and HLA-DQA1*01:02 was driven by IgG4 specific for the Ara h 2 component. Once peanut consumption ceased, the association between IgG4-specific Ara h 2 and HLA-DQA1*01:02 was attenuated. The association was validated by observing expanded IgG4-specific epitopes in people who carried HLA-DQA1*01:02. Notably, we confirmed the previously reported associations with HLA-DQA1*01:02 and peanut allergy risk in the absence of oral peanut protein exposure. Interaction between HLA and presence or absence of exposure to peanut in an allergen- and epitope-specific manner implicates a mechanism of antigen recognition that is fundamental to driving immune responses related to allergy risk or protection.
We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted intervention in the LEAP clinical trial. We identified an association between peanut-specific IgG4 and HLA-DQA1*01:02 that was only observed in the presence of sustained oral peanut protein exposure. The association between IgG4 and HLA-DQA1*01:02 was driven by IgG4 specific for the Ara h 2 component. Once peanut consumption ceased, the association between IgG4-specific Ara h 2 and HLA-DQA1*01:02 was attenuated. The association was validated by observing expanded IgG4-specific epitopes in people who carried HLA-DQA1*01:02. Notably, we confirmed the previously reported associations with HLA-DQA1*01:02 and peanut allergy risk in the absence of oral peanut protein exposure. Interaction between HLA and presence or absence of exposure to peanut in an allergen- and epitope-specific manner implicates a mechanism of antigen recognition that is fundamental to driving immune responses related to allergy risk or protection.We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted intervention in the LEAP clinical trial. We identified an association between peanut-specific IgG4 and HLA-DQA1*01:02 that was only observed in the presence of sustained oral peanut protein exposure. The association between IgG4 and HLA-DQA1*01:02 was driven by IgG4 specific for the Ara h 2 component. Once peanut consumption ceased, the association between IgG4-specific Ara h 2 and HLA-DQA1*01:02 was attenuated. The association was validated by observing expanded IgG4-specific epitopes in people who carried HLA-DQA1*01:02. Notably, we confirmed the previously reported associations with HLA-DQA1*01:02 and peanut allergy risk in the absence of oral peanut protein exposure. Interaction between HLA and presence or absence of exposure to peanut in an allergen- and epitope-specific manner implicates a mechanism of antigen recognition that is fundamental to driving immune responses related to allergy risk or protection.
Audience Academic
Author Grinek, Stepan
Mathias, Rasika A.
Suarez-Farinas, Mayte
Ruczinski, Ingo
Du Toit, George
Sampson, Hugh A.
Lack, Gideon
Cerosaletti, Karen
Bahnson, Henry T.
Nepom, Gerald T.
Kanchan, Kanika
Larson, David
Barnes, Kathleen C.
Shankar, Gautam
AuthorAffiliation 6 The Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology, King’s College London, and Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
8 Department of Pediatrics, Allergy and Immunology and
9 Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA
5 Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
3 Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
4 The Immune Tolerance Network, Bethesda, Maryland, USA
7 The Department of Medicine, University of Colorado, Anschutz, Colorado, USA
1 Division of Allergy and Clinical Immunology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
2 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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MHC class 2
Genetic variation
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Snippet We investigated the interplay between genetics and oral peanut protein exposure in the determination of the immunological response to peanut using the targeted...
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SubjectTerms 2S Albumins, Plant - immunology
Alleles
Allelomorphism
Antibody Formation - genetics
Antibody Formation - immunology
Antigens, Plant - immunology
Arachis
Child
Female
Genetic aspects
Genetics
Health aspects
Histocompatibility antigens
HLA histocompatibility antigens
HLA-DQ alpha-Chains - genetics
HLA-DQ alpha-Chains - immunology
Humans
Immune response
Immunoglobulin G
Immunoglobulin G - immunology
Immunology
Male
Peanut allergy
Peanut Hypersensitivity - genetics
Peanut Hypersensitivity - immunology
Prevention
Title HLA alleles and sustained peanut consumption promote IgG4 responses in subjects protected from peanut allergy
URI https://www.ncbi.nlm.nih.gov/pubmed/34981778
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https://pubmed.ncbi.nlm.nih.gov/PMC8718139
https://doaj.org/article/456cf36dcc204a449920548713ba281d
Volume 132
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