Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope-specific IgE antibody profiling
Author(s)
Type
Journal Article
Abstract
Background: IgE-epitope profiling can accurately diagnose clinical peanut allergy.
Objective: 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.
Methods: 64 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.
Results: In discovery, an algorithm using two ses-IgE antibodies was correlated with CTDs (rho=0.61, p<0.05); this correlation was 0.51 (p<0.05) 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 4 times more likely to tolerate a specific dose, compared to the “low” group. For example, predicted probabilities of tolerating 4, 14, 44 and 144 or 444mg in the “low” group were 92%, 77%, 53%, 29% and 10% compared to 98%, 95%, 94%, 88% and 73% in the “high” group.
Conclusions: 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.
Objective: 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.
Methods: 64 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.
Results: In discovery, an algorithm using two ses-IgE antibodies was correlated with CTDs (rho=0.61, p<0.05); this correlation was 0.51 (p<0.05) 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 4 times more likely to tolerate a specific dose, compared to the “low” group. For example, predicted probabilities of tolerating 4, 14, 44 and 144 or 444mg in the “low” group were 92%, 77%, 53%, 29% and 10% compared to 98%, 95%, 94%, 88% and 73% in the “high” group.
Conclusions: 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.
Date Issued
2022-10-01
Date Acceptance
2022-06-17
Citation
Allergy, 2022, 77 (10), pp.3061-3069
ISSN
0105-4538
Publisher
Wiley
Start Page
3061
End Page
3069
Journal / Book Title
Allergy
Volume
77
Issue
10
Copyright Statement
© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
License URL
Sponsor
Medical Research Council (MRC)
Grant Number
MR/K010468/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
allergy diagnosis
CTD
DBPCFC
epitope
IgE
OFC
peanut allergy
MICROARRAY IMMUNOASSAY
DIAGNOSTIC-ACCURACY
COMPONENTS
CTD
DBPCFC
IgE
OFC
allergy diagnosis
epitope
peanut allergy
Adolescent
Adult
Allergens
Arachis
Child
Child, Preschool
Epitopes
Humans
Immunoglobulin E
Peanut Hypersensitivity
Probability
Young Adult
Humans
Peanut Hypersensitivity
Immunoglobulin E
Allergens
Epitopes
Probability
Adolescent
Adult
Child
Child, Preschool
Young Adult
Arachis
Allergy
1107 Immunology
Publication Status
Published
Date Publish Online
2022-08-12