Biomarkers of severity and threshold of allergic reactions during oral peanut challenges
Biomarkers of severity and threshold of allergic reactions during oral peanut challenges
Background: oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity.
Objective: our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut.
Methods: we assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2–specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC.
Results: when a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2–specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients.
Conclusions: the BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA.
Basophil, LEAP study, adverse events, basophil activation test, diagnosis, food allergy, peanut allergy, severity, threshold
344-355
Santos, Alexandra F.
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Du Toit, George
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O'Rourke, Colin
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Becares, Natalia
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Couto-Francisco, Natalia
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Radulovic, Suzana
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Khaleva, Ekaterina
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Basting, Monica
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Harris, Kristina M.
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Larson, David
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Sayre, Peter
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Plaut, Marshall
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Roberts, Graham
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Bahnson, Henry T.
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Lack, Gideon
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August 2020
Santos, Alexandra F.
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Du Toit, George
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O'Rourke, Colin
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Becares, Natalia
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Couto-Francisco, Natalia
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Radulovic, Suzana
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Khaleva, Ekaterina
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Basting, Monica
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Harris, Kristina M.
a453c645-087b-4031-9c3a-037b45ffe31b
Larson, David
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Sayre, Peter
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Plaut, Marshall
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Roberts, Graham
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Bahnson, Henry T.
2ecc6945-97fd-46bc-8d46-42606d4ccfe0
Lack, Gideon
cac030a2-c358-4880-a91d-d67d06e8e321
Santos, Alexandra F., Du Toit, George, O'Rourke, Colin, Becares, Natalia, Couto-Francisco, Natalia, Radulovic, Suzana, Khaleva, Ekaterina, Basting, Monica, Harris, Kristina M., Larson, David, Sayre, Peter, Plaut, Marshall, Roberts, Graham, Bahnson, Henry T. and Lack, Gideon
(2020)
Biomarkers of severity and threshold of allergic reactions during oral peanut challenges.
Journal of Allergy and Clinical Immunology, 146 (2), .
(doi:10.1016/j.jaci.2020.03.035).
Abstract
Background: oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity.
Objective: our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut.
Methods: we assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2–specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC.
Results: when a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2–specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients.
Conclusions: the BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA.
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Biomarkers of severity
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Accepted/In Press date: 20 March 2020
e-pub ahead of print date: 18 April 2020
Published date: August 2020
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Funding Information:
The research reported in this publication was sponsored by the Immune Tolerance Network and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award UM1AI109565. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support came from the Medical Research Council (MRC Clinical Research Training Fellowship G090218, MRC Clinician Scientist Fellowship MR/M008517/1, and MRC Centenary Early Career Award awarded to A.F. Santos), the Asthma UK Centre, and the UK Department of Health through the National Institute for Health Research Comprehensive Biomedical Research Centre Award to Guy's & St. Thomas? NHS Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust. The Paediatric Allergy clinical trials unit is supported by the National Peanut Board, Atlanta, Ga, and The Davis Foundation. The UK Food Standards Agency provided additional support for the costs of phlebotomy.
Publisher Copyright:
© 2020 The Authors
Keywords:
Basophil, LEAP study, adverse events, basophil activation test, diagnosis, food allergy, peanut allergy, severity, threshold
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Local EPrints ID: 444000
URI: http://eprints.soton.ac.uk/id/eprint/444000
ISSN: 0091-6749
PURE UUID: e042be4f-2396-45ff-a5ff-7f4548fb9cdd
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Date deposited: 21 Sep 2020 17:09
Last modified: 17 Mar 2024 04:02
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Contributors
Author:
Alexandra F. Santos
Author:
George Du Toit
Author:
Colin O'Rourke
Author:
Natalia Becares
Author:
Natalia Couto-Francisco
Author:
Suzana Radulovic
Author:
Ekaterina Khaleva
Author:
Monica Basting
Author:
Kristina M. Harris
Author:
David Larson
Author:
Peter Sayre
Author:
Marshall Plaut
Author:
Henry T. Bahnson
Author:
Gideon Lack
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