Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy.

IF 12.6 1区医学 Q1 ALLERGY Allergy Pub Date : 2024-09-28 DOI:10.1111/all.16341

Noemi Bachmeier-Zbären, Alper Celik, Robin van Brummelen, Nadine Roos, Melanie Steinmann, Jennifer A Hoang, Xiaojun Yin, Christina M Ditlof, Lucy Duan, Julia E M Upton, Thomas Kaufmann, Alexander Eggel, Thomas Eiwegger

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Abstract

Background: Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort.

Methods: Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT.

Results: Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT.

Conclusions: The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood-based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted.

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用于诊断花生过敏的 Hoxb8 肥大细胞活化测试的临床实用性分析。

背景：花生过敏是最严重、最常见的食物过敏之一。诊断对患者及其家人的生活质量有重大影响。有效的管理方法取决于准确、安全和易于实施的诊断方法。我们之前开发了一种基于细胞的检测方法，使用 Hoxb8 肥大细胞（Hoxb8 MCs），旨在改善临床过敏诊断。在本研究中，我们通过测量前瞻性登记和预先验证的花生过敏人群的盲法血清来评估其诊断性能。方法：用花生过敏和花生耐受性儿童和青少年（n = 112）的血清对 Hoxb8 MCs 进行被动致敏。在剂量滴定的花生提取物刺激下，使用流式细胞术量化 Hoxb8 MCs 的脱颗粒现象，并使用 CD107a 作为活化标记。Hoxb8 肥大细胞活化试验（Hoxb8 MAT）的结果与皮肤点刺试验（SPT）、特异性 IgE（sIgE）水平和嗜碱性粒细胞活化试验（BAT）等成熟的诊断方法进行了比较。此外，还用 Hoxb8 MAT 评估了无 BAT 反应者的血清样本：结果：Hoxb8 MAT对花生提取物的激活显示出很强的剂量依赖性，CD107a阳性细胞的临界值为≤5.2%。过敏原浓度≥100 ng/mL时诊断准确性最高，接收者操作特征曲线下面积（AUROC）为0.97，灵敏度为93%，特异性为96%，优于传统的SPT和sIgE检测。与 BAT 相比，Hoxb8 MAT 的诊断效果相当。此外，Hoxb8 MAT 还能准确地将 BAT 无应答者的血清分为过敏者和非过敏者：结论：Hoxb8 MAT 在对花生过敏患者进行前瞻性评估时表现出了很高的诊断精确度，可与基于新鲜全血的 BAT 相媲美。此外，它还证明了其在将 BAT 无应答者准确分类为过敏和非过敏个体方面的价值。我们有必要进一步研究它在常规临床环境中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Allergy 医学-过敏

CiteScore

26.10

自引率

9.70%

发文量

393

审稿时长

2 months

期刊介绍： Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.