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.

中文翻译：

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HLA 等位基因和持续食用花生可促进免受花生过敏的受试者的 IgG4 反应


我们利用 LEAP 临床试验中的针对性干预措施，研究了遗传学和口服花生蛋白暴露之间的相互作用，以确定对花生的免疫反应。我们确定了花生特异性 IgG4 和 HLA-DQA1*01:02 之间的关联，这种关联仅在持续口服花生蛋白的情况下才能观察到。 IgG4 和 HLA-DQA1*01:02 之间的关联是由 Ara h 2 成分特异性的 IgG4 驱动的。一旦停止食用花生，IgG4 特异性 Ara h 2 和 HLA-DQA1*01:02 之间的关联就会减弱。通过观察携带 HLA-DQA1*01:02 的人中扩大的 IgG4 特异性表位，验证了这种关联。值得注意的是，我们证实了之前报道的在没有口服花生蛋白暴露的情况下与 HLA-DQA1*01:02 和花生过敏风险的关联。 HLA 与是否以过敏原和表位特异性方式接触花生之间的相互作用暗示了抗原识别机制，该机制对于驱动与过敏风险或保护相关的免疫反应至关重要。