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 3

Relative distribution of psIgG4 and psIgE, and IgG4 and IgE to peanut components by carrier status.

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Relative distribution of psIgG4 and psIgE, and IgG4 and IgE to peanut co...
(A) HLA-DQA1*01:02 and (B) MALT1 SNP rs57265082. Unadjusted mean values of IgG4 phenotypes stratified by HLA-DQA1*01:02 carrier status and IgE phenotypes stratified by MALT1 carrier status at each assessment and by treatment group assignment are shown with bootstrapped 95% CIs and P values. The associations between IgE and MALT1 are robust to the baseline differences in IgE as previously demonstrated by Winters et al. (8). P values represented are those for the main effect of carrier status, and full results from the model are presented in Supplemental Table 8, A and B. *P < 0.05; **P < 0.0001. The peanut-avoidance and peanut-consumption groups included n = 275 and n = 267 participants, respectively.