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Biomarkers of severity and threshold of allergic reactions during oral peanut challenges

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
0091-6749
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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Santos, Alexandra F.
f5b69586-7f5c-4972-88dd-c463990bda94
Du Toit, George
7930b820-e6f7-4c4c-866c-4334017d1106
O'Rourke, Colin
68ea741f-9df5-4fe1-9d5b-d4a957ab37a7
Becares, Natalia
31f494ad-29e1-480a-900a-4803e8fe7e85
Couto-Francisco, Natalia
6db60cf1-ff9c-47c9-af60-f657d2c7b951
Radulovic, Suzana
8e9bce98-67a2-4999-9898-ccae71e55aa3
Khaleva, Ekaterina
0143fad8-e8b7-4286-997b-368a23488ca8
Basting, Monica
0b4bc8e4-88a3-46d5-80ee-40228ad58c17
Harris, Kristina M.
a453c645-087b-4031-9c3a-037b45ffe31b
Larson, David
032f71e3-99c1-4cd6-a1bc-52ed3f8f976e
Sayre, Peter
d9839665-ad89-43ff-b4fd-1f048446a182
Plaut, Marshall
d6491653-2a2f-4a73-bbfa-cb9b541fac46
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
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), 344-355. (doi:10.1016/j.jaci.2020.03.035).

Record type: Article

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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Accepted/In Press date: 20 March 2020
e-pub ahead of print date: 18 April 2020
Keywords: Basophil, LEAP study, adverse events, basophil activation test, diagnosis, food allergy, peanut allergy, severity, threshold

Identifiers

Local EPrints ID: 444000
URI: http://eprints.soton.ac.uk/id/eprint/444000
ISSN: 0091-6749
PURE UUID: e042be4f-2396-45ff-a5ff-7f4548fb9cdd
ORCID for Graham Roberts: ORCID iD orcid.org/0000-0003-2252-1248

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Date deposited: 21 Sep 2020 17:09
Last modified: 26 Nov 2021 02:49

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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: Graham Roberts ORCID iD
Author: Henry T. Bahnson
Author: Gideon Lack

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