BACKGROUND Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut. OBJECTIVE We sought to determine whether patients who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific IgE profiles than patients who achieved transient desensitization. METHODS Subjects in the POISED trial (NCT02103270) were randomized to peanut (n = 95) or placebo (n = 25) for 24 months. Oral immunotherapy-desensitized subjects were then assigned to no peanut (PN-0) (n = 51) or 300 mg peanut (PN-300) (n = 30) for 12 months. SU and SHT were determined by subjects in PN-0 and PN-300, respectively, passing 4000-mg peanut oral challenge. Specific IgE and IgG4 levels to peanut; Ara h 1, Ara h 2, and Ara h 3 proteins; and 64 allergenic epitopes were measured. We developed machine learning models with bootstrap simulations using baseline data to predict SU/SHT. RESULTS Of 80 (84%) subjects who were desensitized to peanut, 13% (n = 8) and 37% (n = 13) achieved SU/SHT in PN-0 and PN-300 groups. Decreases in epitope-and protein-specific IgE levels and increases in IgG4 levels were observed during 2 years of oral immunotherapy. At baseline, patients with SU in PN-0, but not PN-300, group had lower epitope-specific IgE and protein-specific IgE levels compared with the transient desensitization group. A machine learning model with 12 baseline epitope-specific IgEs and age could predict SU/SHT with accuracy of 94%, area under the curve 0.97, sensitivity 1.00, and specificity 0.91. CONCLUSIONS Subjects who achieved SU/SHT had different baseline protein- and epitope-specific IgE profiles than subjects with transient desensitization. These profiles may help identify patients with an increased likelihood of achieving SU/SHT.

中文翻译：

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在 POISED 试验中，基线表位特异性 IgE 谱可预测口服免疫治疗后 1 年持续无反应或高阈值。


背景 POISED 试验的结果表明，停止花生口服免疫治疗会增加对花生恢复临床反应的风险。目的 我们试图确定达到持续无反应 （SU） 或持续高阈值 （SHT） 的患者是否与达到短暂脱敏的患者具有不同的基线序贯表位特异性 IgE 谱。方法 POISED 试验 （NCT02103270） 中的受试者被随机分配到花生组 （n = 95） 或安慰剂组 （n = 25），为期 24 个月。然后将口服免疫疗法脱敏的受试者分配到无花生 （PN-0） （n = 51） 或 300 毫克花生 （PN-300） （n = 30） 组，持续 12 个月。受试者分别在 PN-0 和 PN-300 中测定 SU 和 SHT，通过 4000 mg 花生口服挑战。花生的特异性 IgE 和 IgG4 水平;Ara h 1、Ara h 2 和 Ara h 3 蛋白;并测量了 64 个过敏原表位。我们使用基线数据开发了带有 bootstrap 模拟的机器学习模型来预测 SU/SHT。结果 在 80 名对花生脱敏的受试者中，13% （n = 8） 和 37% （n = 13） 在 PN-0 和 PN-300 组中实现了 SU/SHT。在口服免疫治疗 2 年期间观察到表位和蛋白质特异性 IgE 水平降低，IgG4 水平升高。基线时，与短暂脱敏组相比，PN-0 组而非 PN-300 组 SU 患者的表位特异性 IgE 和蛋白特异性 IgE 水平较低。具有 12 个基线表位特异性 IgEs 和年龄的机器学习模型可以预测 SU/SHT，准确率为 94%，曲线下面积为 0.97，敏感性为 1.00，特异性为 0.91。结论 达到 SU/SHT 的受试者与短暂脱敏的受试者具有不同的基线蛋白和表位特异性 IgE 谱。 这些概况可能有助于识别实现 SU/SHT 可能性增加的患者。