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

Santos, AF; Du Toit, G; O'Rourke, C; Becares, N; Couto-Francisco, N; Radulovic, S; Khaleva, E; ... Lack, G; + view all (2020) Biomarkers of severity and threshold of allergic reactions during oral peanut challenges. Journal of Allergy and Clinical Immunology , 146 (2) pp. 344-355. 10.1016/j.jaci.2020.03.035. Green open access

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Abstract

BACKGROUND: Oral food challenge (OFC) is the gold-standard to assess peanut allergy (PA) but involves a risk of allergic reactions of unpredictable severity. OBJECTIVE: To identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut. METHODS: We assessed LEAP, LEAP-On and PAS participants with basophil activation test (BAT), skin prick test (SPT), peanut-specific IgE (sIgE) and Ara h 2-sIgE and peanut-specific IgG4 and analyzed the utility of the different biomarkers in relation to PA status, severity and threshold dose of allergic reactions to peanut during OFC. RESULTS: Using a previously defined optimal cut-off, BAT diagnosed PA with 98% specificity and 75% sensitivity. BAT identified severe reactions with 97% specificity and 100% sensitivity. SPT, Ara h 2-sIgE, peanut-sIgE and IgG4/IgE ratios also had 100% sensitivity but slightly lower specificity (92%, 93%, 90% and 88% respectively) to predict severity. Participants with lower threshold of reactivity had higher basophil activation to peanut in vitro. SPT and 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: BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. BAT was the best biomarker for severity, surpassed only by SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to low dose of allergen in individual peanut allergic patients.

Type: Article
Title: Biomarkers of severity and threshold of allergic reactions during oral peanut challenges
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jaci.2020.03.035
Publisher version: https://doi.org/10.1016/j.jaci.2020.03.035
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: LEAP Study, adverse events, basophil, basophil activation test, diagnosis, food allergy, peanut allergy, severity, threshold
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10096861
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