Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope-specific IgE antibody profiling.

Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope-specific IgE antibody profiling.
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DOI:
10.1111/all.15477
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发表时间:
2022-10
期刊:
影响因子:
12.4
通讯作者:
Sampson, Hugh A.
Sampson, Hugh A.
中科院分区:
医学1区
文献类型:
--
作者:
Suprun, Maria;Kearney, Paul;Hayward, Clive;Butler, Heather;Getts, Robert;Sicherer, Scott H.;Turner, Paul J.;Campbell, Dianne E.;Sampson, Hugh A.

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IgE表位分析可准确诊断临床花生过敏。我们试图确定序列(线性)表位特异性IgE (ses - IgE)谱分析是否可以为使用PRACTALL剂量进行双盲、安慰剂对照食物挑战的过敏受试者提供耐受离散剂量花生蛋白的概率。使用基于头的表位测定法对血液样本中的64种se - IgE抗体进行定量。对来自发现队列的75名受试者进行回归分析,确定了一对预测累积耐受剂量(CTD)的ses‐IgEs。该基于表位的预测因子在来自5个独立队列(年龄4-25岁)的331名受试者中得到验证。根据受试者的预测值对其进行分组,并计算每个CTD阈值的反应概率。研究发现,使用两种ses‐IgE抗体的算法与CTDs相关(rho = 0.61, p < 0.05);相关性为0.51 (p <。05)验证。使用基于ses - IgE的预测因子,受试者被分为“高”、“中等”或“低”剂量反应性组。平均而言,“高”组的受试者耐受特定剂量的可能性是“低”组的四倍。例如,“低”组预测耐受4、14、44、144或444毫克的概率分别为92%、77%、53%、29%和10%,而“高”组则为98%、95%、94%、88%和73%。由于各种因素,包括每种剂量有限的应答者样本量和研究特定挑战方案的变化,对食物挑战阈值的准确预测是复杂的。尽管存在这些限制,基于表位的预测因子能够准确地识别ctd,并可能为花生挑战提供有用的替代。本研究评估了ses - IgE谱分析是否可以预测过敏受试者耐受不同剂量花生蛋白的可能性。IgE表位数量与CTDs呈中度负相关。ses - IgE (Ara h 2_008和Ara h 3_100)对CRD的预测效果最好。平均而言,高剂量反应性组的受试者耐受特定剂量的可能性是低剂量组的4倍。缩写:CRD,累积反应剂量;CTD,累积耐受剂量;序列(线性)表位特异性免疫球蛋白E
IgE‐epitope profiling can accurately diagnose clinical peanut allergy. We sought to determine whether sequential (linear) epitope‐specific IgE (ses‐IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double‐blind, placebo‐controlled food challenges utilizing PRACTALL dosing. Sixty four ses‐IgE antibodies were quantified in blood samples using a bead‐based epitope assay. A pair of ses‐IgEs that predicts Cumulative Tolerated Dose (CTD) was determined using regression in 75 subjects from the discovery cohort. This epitope‐based predictor was validated on 331 subjects from five independent cohorts (ages 4–25 years). Subjects were grouped based on their predicted values and probabilities of reactions at each CTD threshold were calculated. In discovery, an algorithm using two ses‐IgE antibodies was correlated with CTDs (rho = 0.61, p < .05); this correlation was 0.51 (p < .05) in validation. Using the ses‐IgE‐based predictor, subjects were assigned into “high,” “moderate,” or “low” dose‐reactivity groups. On average, subjects in the “high” group were four times more likely to tolerate a specific dose, compared with the “low” group. For example, predicted probabilities of tolerating 4, 14, 44, and 144 or 444 mg in the “low” group were 92%, 77%, 53%, 29%, and 10% compared with 98%, 95%, 94%, 88%, and 73% in the “high” group. Accurate predictions of food challenge thresholds are complex due to factors including limited responder sample sizes at each dose and variations in study‐specific challenge protocols. Despite these limitations, an epitope‐based predictor was able to accurately identify CTDs and may provide a useful surrogate for peanut challenges. This study evaluates whether ses‐IgE profiling can predict probability of tolerating discrete doses of peanut protein in allergic subjects.There is a moderate negative correlation between the number of IgE epitopes and CTDs. The pair of ses‐IgE (Ara h 2_008 and Ara h 3_100) provide the best prediction of CRD. On average, subjects in the high‐dose reactivity group are 4 times more likely to tolerate a specific dose, compared to the low‐dose group.Abbreviations: CRD, cumulative reactive dose; CTD, cumulative tolerated dose; ses‐IgE, sequential (linear) epitope‐specific immunoglobulin E
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