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

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Biomarkers of severity and threshold of allergic reactions during oral peanut challenges. / Santos, Alexandra F; Du Toit, George; O'Rourke, Colin; Becares, Natalia; Couto-Francisco, Natália; Radulovic, Suzana; Khaleva, Ekaterina; Basting, Monica; Harris, Kristina M; Larson, David; Sayre, Peter; Plaut, Marshall; Roberts, Graham; Bahnson, Henry T; Lack, Gideon.

In: Journal of Allergy and Clinical Immunology, Vol. 146, No. 2, 08.2020, p. 344-355.

Research output: Contribution to journalArticle

Harvard

Santos, AF, Du Toit, G, O'Rourke, C, Becares, N, Couto-Francisco, N, Radulovic, S, Khaleva, E, Basting, M, Harris, KM, Larson, D, Sayre, P, Plaut, M, Roberts, G, Bahnson, HT & Lack, G 2020, 'Biomarkers of severity and threshold of allergic reactions during oral peanut challenges', Journal of Allergy and Clinical Immunology, vol. 146, no. 2, pp. 344-355. https://doi.org/10.1016/j.jaci.2020.03.035

APA

Santos, A. F., Du Toit, G., O'Rourke, C., Becares, N., Couto-Francisco, N., Radulovic, S., Khaleva, E., Basting, M., Harris, K. M., Larson, D., Sayre, P., Plaut, M., Roberts, G., Bahnson, H. T., & Lack, G. (2020). Biomarkers of severity and threshold of allergic reactions during oral peanut challenges. Journal of Allergy and Clinical Immunology, 146(2), 344-355. https://doi.org/10.1016/j.jaci.2020.03.035

Vancouver

Santos AF, Du Toit G, O'Rourke C, Becares N, Couto-Francisco N, Radulovic S et al. Biomarkers of severity and threshold of allergic reactions during oral peanut challenges. Journal of Allergy and Clinical Immunology. 2020 Aug;146(2):344-355. https://doi.org/10.1016/j.jaci.2020.03.035

Author

Santos, Alexandra F ; Du Toit, George ; O'Rourke, Colin ; Becares, Natalia ; Couto-Francisco, Natália ; Radulovic, Suzana ; Khaleva, Ekaterina ; Basting, Monica ; Harris, Kristina M ; Larson, David ; Sayre, Peter ; Plaut, Marshall ; Roberts, Graham ; Bahnson, Henry T ; Lack, Gideon. / Biomarkers of severity and threshold of allergic reactions during oral peanut challenges. In: Journal of Allergy and Clinical Immunology. 2020 ; Vol. 146, No. 2. pp. 344-355.

Bibtex Download

@article{1e94a18592494a41ad5f00a7ee1a065c,
title = "Biomarkers of severity and threshold of allergic reactions during oral peanut challenges",
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.",
keywords = "Basophil, LEAP study, adverse events, basophil activation test, diagnosis, food allergy, peanut allergy, severity, threshold",
author = "Santos, {Alexandra F} and {Du Toit}, George and Colin O'Rourke and Natalia Becares and Nat{\'a}lia Couto-Francisco and Suzana Radulovic and Ekaterina Khaleva and Monica Basting and Harris, {Kristina M} and David Larson and Peter Sayre and Marshall Plaut and Graham Roberts and Bahnson, {Henry T} and Gideon Lack",
note = "Copyright {\textcopyright} 2020. Published by Elsevier Inc.",
year = "2020",
month = aug,
doi = "10.1016/j.jaci.2020.03.035",
language = "English",
volume = "146",
pages = "344--355",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "MOSBY, INC",
number = "2",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Biomarkers of severity and threshold of allergic reactions during oral peanut challenges

AU - Santos, Alexandra F

AU - Du Toit, George

AU - O'Rourke, Colin

AU - Becares, Natalia

AU - Couto-Francisco, Natália

AU - Radulovic, Suzana

AU - Khaleva, Ekaterina

AU - Basting, Monica

AU - Harris, Kristina M

AU - Larson, David

AU - Sayre, Peter

AU - Plaut, Marshall

AU - Roberts, Graham

AU - Bahnson, Henry T

AU - Lack, Gideon

N1 - Copyright © 2020. Published by Elsevier Inc.

PY - 2020/8

Y1 - 2020/8

N2 - 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.

AB - 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.

KW - Basophil

KW - LEAP study

KW - adverse events

KW - basophil activation test

KW - diagnosis

KW - food allergy

KW - peanut allergy

KW - severity

KW - threshold

UR - http://www.scopus.com/inward/record.url?scp=85086745002&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2020.03.035

DO - 10.1016/j.jaci.2020.03.035

M3 - Article

C2 - 32311390

VL - 146

SP - 344

EP - 355

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 2

ER -

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