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

Lucy Duan; Alper Celik; Jennifer A Hoang; Klara Schmidthaler; Delvin So; Xiaojun Yin; Christina M Ditlof; Marta Ponce; Julia E M Upton; Jean-Soo Lee; Lisa Hung; Heimo Breiteneder; Chiara Palladino; Adelle R Atkinson; Vy H D Kim; Alireza Berenjy; Maria Asper; David Hummel; Samantha Wong; Mara Alexanian-Farr; Ahuva Magder; Sharon R Chinthrajah; Kaori Mukai; Mindy Tsai; Kari Nadeau; Stephen J Galli; Arun K Ramani; Zsolt Szepfalusi; Thomas Eiwegger

doi:10.1111/all.14695

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

Lucy Duan, Alper Celik, Jennifer A Hoang, Klara Schmidthaler, Delvin So, Xiaojun Yin, Christina M Ditlof, Marta Ponce, Julia E M Upton, Jean-Soo Lee, Lisa Hung, Heimo Breiteneder, Chiara Palladino, Adelle R Atkinson, Vy H D Kim, Alireza Berenjy, Maria Asper, David Hummel, Samantha Wong, Mara Alexanian-FarrAhuva Magder, Sharon R Chinthrajah, Kaori Mukai, Mindy Tsai, Kari Nadeau, Stephen J Galli, Arun K Ramani, Zsolt Szepfalusi, Thomas Eiwegger

Research output: Journal article (peer-reviewed) › Journal article

48 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1800-1812
Number of pages	13
Journal	Allergy: European Journal of Allergy and Clinical Immunology
Volume	76
Issue number	6
DOIs	https://doi.org/10.1111/all.14695
Publication status	Published - Jun 2021
Externally published	Yes

Keywords

Allergens
Arachis
Austria
Basophils
Canada
Child
Humans
Nut Hypersensitivity/diagnosis
Nuts
Peanut Hypersensitivity/diagnosis
Skin Tests

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Duan, L., Celik, A., Hoang, J. A., Schmidthaler, K., So, D., Yin, X., Ditlof, C. M., Ponce, M., Upton, J. E. M., Lee, J.-S., Hung, L., Breiteneder, H., Palladino, C., Atkinson, A. R., Kim, V. H. D., Berenjy, A., Asper, M., Hummel, D., Wong, S., ... Eiwegger, T. (2021). Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study. Allergy: European Journal of Allergy and Clinical Immunology, 76(6), 1800-1812. https://doi.org/10.1111/all.14695

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

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.",

keywords = "Allergens, Arachis, Austria, Basophils, Canada, Child, Humans, Nut Hypersensitivity/diagnosis, Nuts, Peanut Hypersensitivity/diagnosis, Skin Tests",

author = "Lucy Duan and Alper Celik and Hoang, {Jennifer A} and Klara Schmidthaler and Delvin So and Xiaojun Yin and Ditlof, {Christina M} and Marta Ponce and Upton, {Julia E M} and Jean-Soo Lee and Lisa Hung and Heimo Breiteneder and Chiara Palladino and Atkinson, {Adelle R} and Kim, {Vy H D} and Alireza Berenjy and Maria Asper and David Hummel and Samantha Wong and Mara Alexanian-Farr and Ahuva Magder and Chinthrajah, {Sharon R} and Kaori Mukai and Mindy Tsai and Kari Nadeau and Galli, {Stephen J} and Ramani, {Arun K} and Zsolt Szepfalusi and Thomas Eiwegger",

note = "Publisher Copyright: {\textcopyright} 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.",

year = "2021",

month = jun,

doi = "10.1111/all.14695",

language = "English",

volume = "76",

pages = "1800--1812",

journal = "Allergy: European Journal of Allergy and Clinical Immunology",

issn = "0105-4538",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

Duan, L, Celik, A, Hoang, JA, Schmidthaler, K, So, D, Yin, X, Ditlof, CM, Ponce, M, Upton, JEM, Lee, J-S, Hung, L, Breiteneder, H, Palladino, C, Atkinson, AR, Kim, VHD, Berenjy, A, Asper, M, Hummel, D, Wong, S, Alexanian-Farr, M, Magder, A, Chinthrajah, SR, Mukai, K, Tsai, M, Nadeau, K, Galli, SJ, Ramani, AK, Szepfalusi, Z & Eiwegger, T 2021, 'Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study', Allergy: European Journal of Allergy and Clinical Immunology, vol. 76, no. 6, pp. 1800-1812. https://doi.org/10.1111/all.14695

TY - JOUR

T1 - Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy

T2 - The Markers of Nut Allergy Study

AU - Duan, Lucy

AU - Celik, Alper

AU - Hoang, Jennifer A

AU - Schmidthaler, Klara

AU - So, Delvin

AU - Yin, Xiaojun

AU - Ditlof, Christina M

AU - Ponce, Marta

AU - Upton, Julia E M

AU - Lee, Jean-Soo

AU - Hung, Lisa

AU - Breiteneder, Heimo

AU - Palladino, Chiara

AU - Atkinson, Adelle R

AU - Kim, Vy H D

AU - Berenjy, Alireza

AU - Asper, Maria

AU - Hummel, David

AU - Wong, Samantha

AU - Alexanian-Farr, Mara

AU - Magder, Ahuva

AU - Chinthrajah, Sharon R

AU - Mukai, Kaori

AU - Tsai, Mindy

AU - Nadeau, Kari

AU - Galli, Stephen J

AU - Ramani, Arun K

AU - Szepfalusi, Zsolt

AU - Eiwegger, Thomas

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

KW - Allergens

KW - Arachis

KW - Austria

KW - Basophils

KW - Canada

KW - Child

KW - Humans

KW - Nut Hypersensitivity/diagnosis

KW - Nuts

KW - Peanut Hypersensitivity/diagnosis

KW - Skin Tests

UR - http://www.scopus.com/inward/record.url?scp=85098110204&partnerID=8YFLogxK

U2 - 10.1111/all.14695

DO - 10.1111/all.14695

M3 - Journal article

C2 - 33300157

SN - 0105-4538

VL - 76

SP - 1800

EP - 1812

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

IS - 6

ER -

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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Keywords

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