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Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy
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  • Alexander Eggel,
  • Noemi Bachmeier-Zbären,
  • Alper Celik,
  • Robin van Brummelen,
  • Jennifer A. Hoang,
  • Xiaojun Yin,
  • Christina Ditlof,
  • Lucy Duan,
  • Julia Upton,
  • Thomas Kaufmann,
  • Thomas Eiwegger
Alexander Eggel
Inselspital Universitatsspital Bern

Corresponding Author:alexander.eggel@unibe.ch

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Noemi Bachmeier-Zbären
Inselspital Universitatsspital Bern
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Alper Celik
SickKids Research Institute
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Robin van Brummelen
Inselspital Universitatsspital Bern
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Jennifer A. Hoang
SickKids Research Institute
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Xiaojun Yin
SickKids Research Institute
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Christina Ditlof
SickKids Research Institute
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Lucy Duan
SickKids Research Institute
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Julia Upton
SickKids Research Institute
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Thomas Kaufmann
Universitat Bern Institut fur Pharmakologie
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Thomas Eiwegger
SickKids Research Institute
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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=96). 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 non-responders were assessed with the Hoxb8 MAT. Results: Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cut-off 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. However, sera from BAT non-responders were accurately classified into allergics and non-allergics 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 blood based BAT. It also demonstrated its value for accurate classification of BAT non-responders into allergic and non-allergic individuals. Further investigations into its utility in the routine clinical setting are warranted.
19 Feb 2024Submitted to Allergy
19 Feb 2024Review(s) Completed, Editorial Evaluation Pending
20 Feb 2024Reviewer(s) Assigned
16 Mar 2024Editorial Decision: Revise Minor
17 Jun 20241st Revision Received
25 Jun 2024Submission Checks Completed
25 Jun 2024Assigned to Editor
12 Jul 2024Reviewer(s) Assigned
23 Jul 2024Review(s) Completed, Editorial Evaluation Pending
07 Aug 2024Editorial Decision: Revise Minor
12 Aug 20242nd Revision Received
14 Aug 2024Submission Checks Completed
14 Aug 2024Assigned to Editor
14 Aug 2024Review(s) Completed, Editorial Evaluation Pending
16 Aug 2024Reviewer(s) Assigned
22 Aug 2024Editorial Decision: Revise Minor
23 Aug 20243rd Revision Received
27 Aug 2024Submission Checks Completed
27 Aug 2024Assigned to Editor
27 Aug 2024Review(s) Completed, Editorial Evaluation Pending
29 Aug 2024Editorial Decision: Accept