Biomarkers of severity and threshold of allergic reactions during oral peanut challenges - 05/08/20
, George Du Toit, MD, FRCPCH a, b, c, ∗, Colin O’Rourke, MS e, ∗, Natalia Becares, PhD a, b, d, Natália Couto-Francisco, MSc a, b, d, Suzana Radulovic, MD a, b, c, Ekaterina Khaleva, MD c, Monica Basting, MA a, b, Kristina M. Harris, PhD f, David Larson, PhD f, Peter Sayre, MD, PhD g, Marshall Plaut, MD h, Graham Roberts, DM, FRCPCH i, j, Henry T. Bahnson, MPH e, Gideon Lack, MD, FRCPCH a, b, c, d, ⁎ 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.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key words : Basophil, basophil activation test, diagnosis, food allergy, LEAP study, peanut allergy, severity, threshold, adverse events
Abbreviations used : Ara h, BAT, CD-sens, fMLP, LEAP, LEAP-On, OFC, PA, PAS, rAra h, SPT
Mappa
| 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. |
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| Disclosure of potential conflict of interest: A. F. Santos reports grants and personal fees from the Medical Research Council (MRC) (MRC Clinical Research Training Fellowship G0902018, MRC Centenary Early Career Award, and MRC Clinician Scientist Fellowship MR/M008517/1); grants from Asthma UK and the National Institute for Health Research (NIHR) through the Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; grants from Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH); grants from Asthma UK; personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; and research support from Buhlmann and Thermo Scientific through a collaboration agreement with King's College London. D. Larson, K. M. Harris, and H. T. Bahnson report grants from the NIAID (NIH grant UM1AI109565). G. Du Toit reports grants from the NIAID of the NIH, Food Allergy & Research Education, UK Department of Health through NIHR, National Peanut Board (NPB), and UK Food Standards Agency; these grants partly funded salary over the period of this submitted work. G. Lack reports grants from the NIAID of the NIH (grants NO1-AI-15416 and UM1AI109565), Food Allergy & Research Education, the National Institute for Health Research through a Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, National Peanut Board, UK Food Standards Agency, and Davis Foundation, as well as personal fees from Novartis, Aravax, ALK-Abelló, DBV Technologies, and Mighty Mission Me. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 146 - N° 2
P. 344-355 - Agosto 2020 Ritorno al numero
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