HLA alleles and sustained peanut consumption promote IgG4 responses in subjects protected from peanut allergy
Kanika Kanchan, … , Karen Cerosaletti, Rasika A. Mathias
Kanika Kanchan, … , Karen Cerosaletti, Rasika A. Mathias
Published January 4, 2022
Citation Information: J Clin Invest. 2022;132(1):e152070. https://doi.org/10.1172/JCI152070.
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Research Article Genetics Immunology

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

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.

Authors

Kanika Kanchan, Stepan Grinek, Henry T. Bahnson, Ingo Ruczinski, Gautam Shankar, David Larson, George Du Toit, Kathleen C. Barnes, Hugh A. Sampson, Mayte Suarez-Farinas, Gideon Lack, Gerald T. Nepom, Karen Cerosaletti, Rasika A. Mathias

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Figure 4

Expansion of linear epitopes in ses-IgG4 and ses-IgE at 60 months versus baseline visit.

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Expansion of linear epitopes in ses-IgG4 and ses-IgE at 60 months versus...
(A and B) Bars represent the changes in binding from baseline to 60-month visit in log2 fold change. Red indicates significant expansion (FDR < 0.05); asterisks indicate significance in differences between the 2 genotypes, carrier (HLA+ and MALT1+ panels) and noncarrier (HLA– and MALT1– panels): *FDR < 0.05; **FDR < 0.01; ***FDR < 0.001; †FDR < 0.1. (A) ses-IgG4 expansion by HLA-DQA1*01:02 genotype among children (n = 161) in the peanut-consumption group who became sensitized by visits at 60 months. (B) ses-IgE expansion by MALT1 genotype status in children enrolled in the avoidance group (n = 162) who developed PA after 60 months and (C) ses-IgG4 Ara h 2.008 epitope expansion by HLA-DQA1*01:02 in sensitized versus nonsensitized, nonallergic subjects in the consumption group (carriers, blue; noncarriers, red); asterisks indicate significance in differences between the 2 genotypes as in A and B. Error bars in all panels correspond to CIs. Data are represented as mean ± 95%CI.