BACKGROUND Oral immunotherapy (OIT) can successfully desensitize many peanut-allergic subjects, but clinical tolerance diminishes over time on discontinuation, or low-dose maintenance, of peanut. Therefore, to improve the efficacy and sustainability of such therapy, we sought to identify biomarkers and clinical tools that can predict therapeutic outcomes and monitor treatment responses. OBJECTIVE We evaluated whether basophil activation in whole blood, and plasma levels of peanut-specific immunoglobulins, are useful biomarkers for peanut OIT. METHODS We longitudinally measured, before, during, and after OIT, basophil activation in whole blood ex vivo in response to peanut stimulation, and peanut-specific IgE (sIgE) and peanut-specific IgG4 (sIgG4), in a large, single-site, double-blind, randomized, placebo-controlled, phase 2 peanut OIT study. We compared basophil responsiveness and peanut-specific immunoglobulins between those who were clinically reactive and those who were tolerant to peanut oral challenges. RESULTS Peanut OIT significantly decreased basophil activation, peanut sIgE, Ara h 1, Ara h 2, and Ara h 3 IgE levels, and sIgE/total IgE, but increased sIgG4/sIgE. Participants who became reactive to 4 g of peanut 13 weeks off active OIT exhibited higher peanut-induced basophil activation ex vivo and higher peanut sIgE levels and sIgE/total IgE, but lower sIgG4/sIgE. Notably, participants entering the study with low basophil responsiveness were more likely to achieve treatment success. Substantial suppression of basophil activation was required to maintain long-term clinical tolerance after peanut OIT. CONCLUSIONS Assessments of peanut-induced basophil activation and peanut-specific immunoglobulins can help to predict treatment outcomes, and to differentiate transient desensitization versus sustained unresponsiveness after OIT.

中文翻译：

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持续成功的花生口服免疫疗法与低嗜碱性粒细胞活化和花生特异性 IgE 相关。

背景口服免疫疗法（OIT）可以成功地使许多花生过敏受试者脱敏，但随着时间的推移，停止或低剂量维持花生后，临床耐受性会降低。因此，为了提高此类疗法的功效和可持续性，我们寻求确定可以预测治疗结果和监测治疗反应的生物标志物和临床工具。目的 我们评估全血中嗜碱性粒细胞的活化和花生特异性免疫球蛋白的血浆水平是否是花生 OIT 的有用生物标志物。方法 我们在 OIT 之前、期间和之后纵向测量了离体全血中响应花生刺激的嗜碱性粒细胞活化情况，以及花生特异性 IgE (sIgE) 和花生特异性 IgG4 (sIgG4)。 ，双盲，随机，安慰剂对照，2 期花生 OIT 研究。我们比较了临床反应性患者和对花生口服挑战耐受的患者之间的嗜碱性粒细胞反应性和花生特异性免疫球蛋白。结果花生 OIT 显着降低嗜碱性粒细胞活化、花生 sIgE、Ara h 1、Ara h 2 和 Ara h 3 IgE 水平以及 sIgE/总 IgE，但增加 sIgG4/sIgE。停止活性 OIT 13 周后对 4 g 花生产生反应的参与者表现出较高的花生诱导的离体嗜碱性粒细胞活化以及较高的花生 sIgE 水平和 sIgE/总 IgE，但 sIgG4/sIgE 较低。值得注意的是，参与研究的嗜碱性粒细胞反应性较低的参与者更有可能获得治疗成功。花生 OIT 后需要大量抑制嗜碱性粒细胞活化才能维持长期临床耐受性。结论 对花生诱导的嗜碱性粒细胞活化和花生特异性免疫球蛋白的评估有助于预测治疗结果，并区分 OIT 后短暂脱敏与持续无反应。