Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study

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 investiga...

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Veröffentlicht in:Allergy (Copenhagen) 2021-06, Vol.76 (6), p.1800-1812
Hauptverfasser: Duan, Lucy, Celik, Alper, Hoang, Jennifer A., Schmidthaler, Klara, So, Delvin, Yin, Xiaojun, Ditlof, Christina M., Ponce, Marta, Upton, Julia E.M., Lee, Jean‐Soo, Hung, Lisa, Breiteneder, Heimo, Palladino, Chiara, Atkinson, Adelle R., Kim, Vy H.D., Berenjy, Alireza, Asper, Maria, Hummel, David, Wong, Samantha, Alexanian‐Farr, Mara, Magder, Ahuva, Chinthrajah, Sharon R., Mukai, Kaori, Tsai, Mindy, Nadeau, Kari, Galli, Stephen J., Ramani, Arun K., Szepfalusi, Zsolt, Eiwegger, Thomas
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container_issue 6
container_start_page 1800
container_title Allergy (Copenhagen)
container_volume 76
creator Duan, Lucy
Celik, Alper
Hoang, Jennifer A.
Schmidthaler, Klara
So, Delvin
Yin, Xiaojun
Ditlof, Christina M.
Ponce, Marta
Upton, Julia E.M.
Lee, Jean‐Soo
Hung, Lisa
Breiteneder, Heimo
Palladino, Chiara
Atkinson, Adelle R.
Kim, Vy H.D.
Berenjy, Alireza
Asper, Maria
Hummel, David
Wong, Samantha
Alexanian‐Farr, Mara
Magder, Ahuva
Chinthrajah, Sharon R.
Mukai, Kaori
Tsai, Mindy
Nadeau, Kari
Galli, Stephen J.
Ramani, Arun K.
Szepfalusi, Zsolt
Eiwegger, Thomas
description 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. BAT can predict allergic clinical status to peanut and individual tree nuts in multi‐nut‐sensitized children from Austria and Canada. Mixed effect model integrating 10 and 100 ng/mL of peanut and individual tree nut stimulation is effective in diagnosing allergy. BAT separates allergic from non‐allergic status in patients who underwent clinically indicated OFCs to peanut and individual tree nuts. Abbreviations: BAT, basophil activation test; OFC, oral food challenge; sIgE, specific IgE.
doi_str_mv 10.1111/all.14695
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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. BAT can predict allergic clinical status to peanut and individual tree nuts in multi‐nut‐sensitized children from Austria and Canada. Mixed effect model integrating 10 and 100 ng/mL of peanut and individual tree nut stimulation is effective in diagnosing allergy. BAT separates allergic from non‐allergic status in patients who underwent clinically indicated OFCs to peanut and individual tree nuts. Abbreviations: BAT, basophil activation test; OFC, oral food challenge; sIgE, specific IgE.</description><identifier>ISSN: 0105-4538</identifier><identifier>EISSN: 1398-9995</identifier><identifier>DOI: 10.1111/all.14695</identifier><identifier>PMID: 33300157</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Allergens ; Allergies ; allergy diagnosis ; Anacardiaceae ; Anaphylaxis ; Arachis ; Austria ; basophil ; Basophils ; Canada ; CD63 antigen ; challenge tests ; Child ; Diagnostic tests ; Food allergies ; food allergy ; Humans ; Immunoglobulin E ; Leukocytes (basophilic) ; Mathematical models ; Medical diagnosis ; molecular allergology ; multiple nut allergy ; Nut Hypersensitivity - diagnosis ; Nuts ; Patients ; Peanut Hypersensitivity - diagnosis ; Pediatrics ; Skin Tests</subject><ispartof>Allergy (Copenhagen), 2021-06, Vol.76 (6), p.1800-1812</ispartof><rights>2020 EAACI and John Wiley and Sons A/S. 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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. BAT can predict allergic clinical status to peanut and individual tree nuts in multi‐nut‐sensitized children from Austria and Canada. Mixed effect model integrating 10 and 100 ng/mL of peanut and individual tree nut stimulation is effective in diagnosing allergy. BAT separates allergic from non‐allergic status in patients who underwent clinically indicated OFCs to peanut and individual tree nuts. 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Celik, Alper ; Hoang, Jennifer A. ; Schmidthaler, Klara ; So, Delvin ; Yin, Xiaojun ; Ditlof, Christina M. ; Ponce, Marta ; Upton, Julia E.M. ; Lee, Jean‐Soo ; Hung, Lisa ; Breiteneder, Heimo ; Palladino, Chiara ; Atkinson, Adelle R. ; Kim, Vy H.D. ; Berenjy, Alireza ; Asper, Maria ; Hummel, David ; Wong, Samantha ; Alexanian‐Farr, Mara ; Magder, Ahuva ; Chinthrajah, Sharon R. ; Mukai, Kaori ; Tsai, Mindy ; Nadeau, Kari ; Galli, Stephen J. ; Ramani, Arun K. ; Szepfalusi, Zsolt ; Eiwegger, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4435-3d5fab8a2d64e6d60a4f5c08681438834478df68923b1a174a8913f9bf95631e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Allergens</topic><topic>Allergies</topic><topic>allergy diagnosis</topic><topic>Anacardiaceae</topic><topic>Anaphylaxis</topic><topic>Arachis</topic><topic>Austria</topic><topic>basophil</topic><topic>Basophils</topic><topic>Canada</topic><topic>CD63 antigen</topic><topic>challenge tests</topic><topic>Child</topic><topic>Diagnostic tests</topic><topic>Food allergies</topic><topic>food allergy</topic><topic>Humans</topic><topic>Immunoglobulin E</topic><topic>Leukocytes (basophilic)</topic><topic>Mathematical models</topic><topic>Medical diagnosis</topic><topic>molecular allergology</topic><topic>multiple nut allergy</topic><topic>Nut Hypersensitivity - diagnosis</topic><topic>Nuts</topic><topic>Patients</topic><topic>Peanut Hypersensitivity - diagnosis</topic><topic>Pediatrics</topic><topic>Skin Tests</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duan, Lucy</creatorcontrib><creatorcontrib>Celik, Alper</creatorcontrib><creatorcontrib>Hoang, Jennifer A.</creatorcontrib><creatorcontrib>Schmidthaler, Klara</creatorcontrib><creatorcontrib>So, Delvin</creatorcontrib><creatorcontrib>Yin, Xiaojun</creatorcontrib><creatorcontrib>Ditlof, Christina M.</creatorcontrib><creatorcontrib>Ponce, Marta</creatorcontrib><creatorcontrib>Upton, Julia E.M.</creatorcontrib><creatorcontrib>Lee, Jean‐Soo</creatorcontrib><creatorcontrib>Hung, Lisa</creatorcontrib><creatorcontrib>Breiteneder, Heimo</creatorcontrib><creatorcontrib>Palladino, Chiara</creatorcontrib><creatorcontrib>Atkinson, Adelle R.</creatorcontrib><creatorcontrib>Kim, Vy H.D.</creatorcontrib><creatorcontrib>Berenjy, Alireza</creatorcontrib><creatorcontrib>Asper, Maria</creatorcontrib><creatorcontrib>Hummel, David</creatorcontrib><creatorcontrib>Wong, Samantha</creatorcontrib><creatorcontrib>Alexanian‐Farr, Mara</creatorcontrib><creatorcontrib>Magder, Ahuva</creatorcontrib><creatorcontrib>Chinthrajah, Sharon R.</creatorcontrib><creatorcontrib>Mukai, Kaori</creatorcontrib><creatorcontrib>Tsai, Mindy</creatorcontrib><creatorcontrib>Nadeau, Kari</creatorcontrib><creatorcontrib>Galli, Stephen J.</creatorcontrib><creatorcontrib>Ramani, Arun K.</creatorcontrib><creatorcontrib>Szepfalusi, Zsolt</creatorcontrib><creatorcontrib>Eiwegger, Thomas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Allergy (Copenhagen)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duan, Lucy</au><au>Celik, Alper</au><au>Hoang, Jennifer A.</au><au>Schmidthaler, Klara</au><au>So, Delvin</au><au>Yin, Xiaojun</au><au>Ditlof, Christina M.</au><au>Ponce, Marta</au><au>Upton, Julia E.M.</au><au>Lee, Jean‐Soo</au><au>Hung, Lisa</au><au>Breiteneder, Heimo</au><au>Palladino, Chiara</au><au>Atkinson, Adelle R.</au><au>Kim, Vy H.D.</au><au>Berenjy, Alireza</au><au>Asper, Maria</au><au>Hummel, David</au><au>Wong, Samantha</au><au>Alexanian‐Farr, Mara</au><au>Magder, Ahuva</au><au>Chinthrajah, Sharon R.</au><au>Mukai, Kaori</au><au>Tsai, Mindy</au><au>Nadeau, Kari</au><au>Galli, Stephen J.</au><au>Ramani, Arun K.</au><au>Szepfalusi, Zsolt</au><au>Eiwegger, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study</atitle><jtitle>Allergy (Copenhagen)</jtitle><addtitle>Allergy</addtitle><date>2021-06</date><risdate>2021</risdate><volume>76</volume><issue>6</issue><spage>1800</spage><epage>1812</epage><pages>1800-1812</pages><issn>0105-4538</issn><eissn>1398-9995</eissn><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. BAT can predict allergic clinical status to peanut and individual tree nuts in multi‐nut‐sensitized children from Austria and Canada. Mixed effect model integrating 10 and 100 ng/mL of peanut and individual tree nut stimulation is effective in diagnosing allergy. BAT separates allergic from non‐allergic status in patients who underwent clinically indicated OFCs to peanut and individual tree nuts. Abbreviations: BAT, basophil activation test; OFC, oral food challenge; sIgE, specific IgE.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>33300157</pmid><doi>10.1111/all.14695</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-0560-583X</orcidid><orcidid>https://orcid.org/0000-0002-2146-2955</orcidid><orcidid>https://orcid.org/0000-0003-2022-8689</orcidid><orcidid>https://orcid.org/0000-0001-5320-4232</orcidid><orcidid>https://orcid.org/0000-0001-9620-0303</orcidid><orcidid>https://orcid.org/0000-0003-4852-3102</orcidid><orcidid>https://orcid.org/0000-0003-2467-4256</orcidid><orcidid>https://orcid.org/0000-0002-2914-7829</orcidid><orcidid>https://orcid.org/0000-0001-9264-1881</orcidid><orcidid>https://orcid.org/0000-0001-5736-5340</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0105-4538
ispartof Allergy (Copenhagen), 2021-06, Vol.76 (6), p.1800-1812
issn 0105-4538
1398-9995
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8608143
source Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals
subjects Allergens
Allergies
allergy diagnosis
Anacardiaceae
Anaphylaxis
Arachis
Austria
basophil
Basophils
Canada
CD63 antigen
challenge tests
Child
Diagnostic tests
Food allergies
food allergy
Humans
Immunoglobulin E
Leukocytes (basophilic)
Mathematical models
Medical diagnosis
molecular allergology
multiple nut allergy
Nut Hypersensitivity - diagnosis
Nuts
Patients
Peanut Hypersensitivity - diagnosis
Pediatrics
Skin Tests
title Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study
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