Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.
Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.
复制标题
花生过敏儿童花生表皮免疫治疗的免疫反应演变。
DOI：
10.1111/all.15709
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发表时间：
2023
期刊：
影响因子：
12.4
通讯作者：
Greenhawt,Matthew
中科院分区：
文献类型：
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作者：
Bastin,Marie;Carr,WarnerW;Davis,CarlaM;Fleischer,DavidM;Lieberman,JayA;Mustafa,SShahzad;Helleputte,Thibault;Bois,Timothée;Campbell,DianneE;Green,ToddD;Greenhawt,Matthew
研究背景：在临床试验中，使用Viaskin™花生250 μg （DBV712）进行皮肤免疫治疗的花生过敏儿童的脱敏效果在统计学上优于安慰剂。目前尚不清楚血清学生物标志物是否能预测反应。方法采用探索性单因素和多因素分析，根据第12个月(M)双盲安慰剂对照食物刺激时的花生蛋白诱导剂量（ED），对参加IgE介导花生过敏儿童Viaskin花生3期疗效和安全性研究的受试者的血清特异性IgG4和IgE（全花生及其成分）进行检测，以确定治疗反应的轨迹和预测因素。结果在经Viaskin花生处理的受试者中，花生sIgG4从基线到M12显著增加，花生sIgE在M3时达到峰值，在M12时降至基线以下，花生sIgG4和sIgE成分反映了这些轨迹。安慰剂组没有明显的变化。单因素分析显示，M12花生sIgG4/sIgE在治疗应答者中较高（p< 0.001），预测ED≥300 mg和≥1000 mg的曲线下面积（AUC）最高（AUC分别为69.5%和69.9%）。M12花生sIgG4/sIgE >20.1预测M12 ED≥300 mg（80%阳性预测值）。表现最好的组分为α 1 sIgE <15.7 kUA/L （AUC为66.5%）。花生sIgG4/sIgE与Ara h 1的多变量模型的AUC分别为68.2% （ED≥300 mg）和67.8% （ED≥1000 mg）。结论血清sIgG4升高与安慰剂组差异最明显。sIgG4/sIgE比值>20.1以及花生和花生的sIgG4/sIgE组合预测治疗反应的能力中等，可能对临床监测有用。需要更多的数据来证实这些关系。
BackgroundEpicutaneous immunotherapy with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut‐allergic children in clinical trials. It is unclear whether serologic biomarkers predict response.MethodsSerum‐specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE‐Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double‐blind placebo‐controlled food challenge.ResultsAmong Viaskin Peanut‐treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p< 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA/L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg).ConclusionsPeanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.