Lucy Duan1,2, Alper Celik3, Jennifer A Hoang1, Klara Schmidthaler4, Delvin So3, Xiaojun Yin1, Christina M Ditlof1,5, Marta Ponce4, Julia E M Upton2, Jean-Soo Lee1, Lisa Hung1,5, Heimo Breiteneder6, Chiara Palladino6, Adelle R Atkinson2, Vy H D Kim2, Alireza Berenjy1, Maria Asper2, David Hummel2, Samantha Wong2, Mara Alexanian-Farr2, Ahuva Magder2, Sharon R Chinthrajah7,8, Kaori Mukai7, Mindy Tsai9, Kari Nadeau7,8,10, Stephen J Galli7,9, Arun K Ramani2, Zsolt Szepfalusi3, Thomas Eiwegger1,2,4. 1. Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada. 2. Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada. 3. Centre for Computational Medicine, Hospital for Sick Children, Toronto, ON, Canada. 4. Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. 5. Department of Immunology, University of Toronto, Toronto, ON, Canada. 6. Division of Medical Biotechnology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. 7. Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, USA. 8. Division of Allergy, Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA. 9. Departments of Pathology and of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. 10. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
Abstract
BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE. RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC. CONCLUSIONS: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.
BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE. RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC. CONCLUSIONS: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.
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