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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:146

Article

Santos, Alexandra F.^1,2,3,4  Du Toit, George^1,2,3  O'Rourke, Colin⁵  Becares, Natalia^1,2,4  Couto-Francisco, Natalia^1,2,4  Radulovic, Suzana^1,2,3  Khaleva, Ekaterina³  Basting, Monica^1,2  Harris, Kristina M.⁶  Larson, David⁶  Sayre, Peter⁷  Plaut, Marshall⁸  Roberts, Graham^9,10,11  Bahnson, Henry T.⁵  Lack, Gideon^1,2,3,4 

[1] Kings Coll London, Dept Women & Childrens Hlth Pediat Allergy, Sch Life Course Sci, Fac Life Sci & Med, London, England

[2] Kings Coll London, Peter Gorer Dept Immunobiol, Sch Immunol & Microbial Sci, London, England

[3] Guys & St Thomas Hosp, Evelina London Childrens Hosp, Childrens Allergy Serv, London, England

[4] Asthma UK Ctr Allerg Mechanisms Asthma, London, England

[5] Benaroya Res Inst, Immune Tolerance Network, Seattle, WA USA

[6] Immune Tolerance Network, Bethesda, MD USA

[7] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA

[8] Natl Inst Allergy & Infect Dis, Bethesda, MD USA

[9] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England

[10] Univ Southampton, Natl Inst Hlth Res, Biomed Res Ctr, Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England

[11] Univ Southampton, Fac Med, Clin & Expt Sci Acad Unit, Southampton, Hants, England

关键词: Basophil;    basophil activation test;    diagnosis;    food allergy;    LEAP study;    peanut allergy;    severity;    threshold;    adverse events;   

DOI  :  10.1016/j.jaci.2020.03.035

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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