Ara h 2-Specific IgE Presence Rather Than Its Function Is the Best Predictor of Mast Cell Activation in Children

Chen Ji; Yue Huang; Long Him Yeung; Oliver Hemmings; Zainab Jama; Matthew Kwok; Gideon Lack; Alexandra F. Santos

doi:10.1016/j.jaip.2022.12.026

Ara h 2-Specific IgE Presence Rather Than Its Function Is the Best Predictor of Mast Cell Activation in Children

Chen Ji, Yue Huang, Long Him Yeung, Oliver Hemmings, Zainab Jama, Matthew Kwok, Gideon Lack, Alexandra F. Santos^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Background: Ara h 2-specific IgE (Arah2-sIgE) is an excellent serologic marker for peanut allergy. However, not all subjects with detectable Arah2-sIgE react clinically. Objective: To assess the importance of functional characteristics of Arah2-sIgE for Ara h 2-induced mast cell activation. Methods: We studied a cohort of children assessed for peanut allergy. We determined Arah2-sIgE levels, Ara h 2/total IgE ratios and IgE avidity for Ara h 2 using ImmunoCAP (Thermo Fisher) and mast cell activation to Ara h 2 using flow cytometry. Results: Samples from 61 of 100 children (46 peanut-allergic [PA] and 15 peanut-sensitized tolerant) who had Arah2-sIgE levels 0.10 kU/L or greater were studied. Arah2-sIgE and Ara h 6-specific IgE levels, Ara h 2/total IgE ratios, and the diversity of IgE for Ara h 2 epitopes were higher in PA compared with peanut-sensitized tolerant samples. The levels of IgE to peanut, Ara h 1, and Ara h 3 were not significantly different between groups. Results from the mast cell activation test to Ara h 2 strongly correlated with Arah2-sIgE levels (r = 0.722; P < .001) and Ara h 2/total IgE ratios (r = 0.697; P < .001) and moderately with Arah2-sIgE diversity (r = 0.540; P < .001). On a linear regression model, Arah2-sIgE levels (standardized β-coefficient = 0.396; P = .008) and Ara h 2/total IgE ratios (standardized β-coefficient = 0.0.669; P = .002) were the main determinants of mast cell response to Ara h 2. Conclusions: Most children sensitized to Ara h 2 are PA. Ara h 2-specific IgE titers and specific activity are the major determinants of mast cell response to Ara h 2.

Original language	English
Pages (from-to)	1154-1161.e3
Journal	Journal of Allergy and Clinical Immunology: In Practice
Volume	11
Issue number	4
DOIs	https://doi.org/10.1016/j.jaip.2022.12.026
Publication status	Published - Apr 2023

Keywords

Anaphylaxis
Ara h 2
Food allergy
IgE
Mast cell activation
Mast cells
Peanut allergy

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10.1016/j.jaip.2022.12.026

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@article{978dbd105f564797bad728d76c10b221,

title = "Ara h 2-Specific IgE Presence Rather Than Its Function Is the Best Predictor of Mast Cell Activation in Children",

abstract = "Background: Ara h 2-specific IgE (Arah2-sIgE) is an excellent serologic marker for peanut allergy. However, not all subjects with detectable Arah2-sIgE react clinically. Objective: To assess the importance of functional characteristics of Arah2-sIgE for Ara h 2-induced mast cell activation. Methods: We studied a cohort of children assessed for peanut allergy. We determined Arah2-sIgE levels, Ara h 2/total IgE ratios and IgE avidity for Ara h 2 using ImmunoCAP (Thermo Fisher) and mast cell activation to Ara h 2 using flow cytometry. Results: Samples from 61 of 100 children (46 peanut-allergic [PA] and 15 peanut-sensitized tolerant) who had Arah2-sIgE levels 0.10 kU/L or greater were studied. Arah2-sIgE and Ara h 6-specific IgE levels, Ara h 2/total IgE ratios, and the diversity of IgE for Ara h 2 epitopes were higher in PA compared with peanut-sensitized tolerant samples. The levels of IgE to peanut, Ara h 1, and Ara h 3 were not significantly different between groups. Results from the mast cell activation test to Ara h 2 strongly correlated with Arah2-sIgE levels (r = 0.722; P < .001) and Ara h 2/total IgE ratios (r = 0.697; P < .001) and moderately with Arah2-sIgE diversity (r = 0.540; P < .001). On a linear regression model, Arah2-sIgE levels (standardized β-coefficient = 0.396; P = .008) and Ara h 2/total IgE ratios (standardized β-coefficient = 0.0.669; P = .002) were the main determinants of mast cell response to Ara h 2. Conclusions: Most children sensitized to Ara h 2 are PA. Ara h 2-specific IgE titers and specific activity are the major determinants of mast cell response to Ara h 2.",

keywords = "Anaphylaxis, Ara h 2, Food allergy, IgE, Mast cell activation, Mast cells, Peanut allergy",

author = "Chen Ji and Yue Huang and Yeung, {Long Him} and Oliver Hemmings and Zainab Jama and Matthew Kwok and Gideon Lack and Santos, {Alexandra F.}",

note = "Funding Information: The authors wish to thank Professor George Du Toit, Dr Suzana Radulovic, and the Paediatric Allergy Team at the Evelina London Children{\textquoteright}s Hospital for their effort in recruiting participants and collecting samples for the study; and they acknowledge support from the UK National Institute for Health Research Comprehensive Biomedical Research Centre Award to Guy{\textquoteright}s and St Thomas{\textquoteright} National Health Service Foundation Trust, in partnership with the King{\textquoteright}s College London and King{\textquoteright}s College Hospital National Health Service Foundation Trust. Funding Information: This work was supported by the Medical Research Council (Fellowships MR/T032081/1, MR/M008517/1, and G0902018, awarded to A.F. Santos) and Asthma UK (AUK-BC-2015-01) and by the UK National Institute for Health Research Comprehensive Biomedical Research Centre award to Guy's and St Thomas{\textquoteright} National Health Service Foundation Trust, in partnership with the King's College London and King's College Hospital National Health Service Foundation Trust.Conflicts of interest: A.F. Santos reports grants and personal fees from the Medical Research Council (MR/T032081/1)); grants from Asthma UK, Immune Tolerance Network/National Institute of Allergy and Infectious Diseases, BBSRC, Rosetrees Trust and Food Allergy Research and Education (FARE); personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; as well as research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Conflicts of interest: A.F. Santos reports grants and personal fees from the Medical Research Council (MR/T032081/1)); grants from Asthma UK, Immune Tolerance Network /National Institute of Allergy and Infectious Diseases, BBSRC, Rosetrees Trust and Food Allergy Research and Education (FARE); personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; as well as research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London . The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: This work was supported by the Medical Research Council (Fellowships MR/T032081/1, MR/M008517/1, and G0902018, awarded to A.F. Santos) and Asthma UK (AUK-BC-2015-01) and by the UK National Institute for Health Research Comprehensive Biomedical Research Centre award to Guy{\textquoteright}s and St Thomas{\textquoteright} National Health Service Foundation Trust, in partnership with the King{\textquoteright}s College London and King{\textquoteright}s College Hospital National Health Service Foundation Trust. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2023",

month = apr,

doi = "10.1016/j.jaip.2022.12.026",

language = "English",

volume = "11",

pages = "1154--1161.e3",

journal = "Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Ara h 2-Specific IgE Presence Rather Than Its Function Is the Best Predictor of Mast Cell Activation in Children

AU - Ji, Chen

AU - Huang, Yue

AU - Yeung, Long Him

AU - Hemmings, Oliver

AU - Jama, Zainab

AU - Kwok, Matthew

AU - Lack, Gideon

AU - Santos, Alexandra F.

N1 - Funding Information: The authors wish to thank Professor George Du Toit, Dr Suzana Radulovic, and the Paediatric Allergy Team at the Evelina London Children’s Hospital for their effort in recruiting participants and collecting samples for the study; and they acknowledge support from the UK National Institute for Health Research Comprehensive Biomedical Research Centre Award to Guy’s and St Thomas’ National Health Service Foundation Trust, in partnership with the King’s College London and King’s College Hospital National Health Service Foundation Trust. Funding Information: This work was supported by the Medical Research Council (Fellowships MR/T032081/1, MR/M008517/1, and G0902018, awarded to A.F. Santos) and Asthma UK (AUK-BC-2015-01) and by the UK National Institute for Health Research Comprehensive Biomedical Research Centre award to Guy's and St Thomas’ National Health Service Foundation Trust, in partnership with the King's College London and King's College Hospital National Health Service Foundation Trust.Conflicts of interest: A.F. Santos reports grants and personal fees from the Medical Research Council (MR/T032081/1)); grants from Asthma UK, Immune Tolerance Network/National Institute of Allergy and Infectious Diseases, BBSRC, Rosetrees Trust and Food Allergy Research and Education (FARE); personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; as well as research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Conflicts of interest: A.F. Santos reports grants and personal fees from the Medical Research Council (MR/T032081/1)); grants from Asthma UK, Immune Tolerance Network /National Institute of Allergy and Infectious Diseases, BBSRC, Rosetrees Trust and Food Allergy Research and Education (FARE); personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; as well as research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London . The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: This work was supported by the Medical Research Council (Fellowships MR/T032081/1, MR/M008517/1, and G0902018, awarded to A.F. Santos) and Asthma UK (AUK-BC-2015-01) and by the UK National Institute for Health Research Comprehensive Biomedical Research Centre award to Guy’s and St Thomas’ National Health Service Foundation Trust, in partnership with the King’s College London and King’s College Hospital National Health Service Foundation Trust. Publisher Copyright: © 2022 The Authors

PY - 2023/4

Y1 - 2023/4

N2 - Background: Ara h 2-specific IgE (Arah2-sIgE) is an excellent serologic marker for peanut allergy. However, not all subjects with detectable Arah2-sIgE react clinically. Objective: To assess the importance of functional characteristics of Arah2-sIgE for Ara h 2-induced mast cell activation. Methods: We studied a cohort of children assessed for peanut allergy. We determined Arah2-sIgE levels, Ara h 2/total IgE ratios and IgE avidity for Ara h 2 using ImmunoCAP (Thermo Fisher) and mast cell activation to Ara h 2 using flow cytometry. Results: Samples from 61 of 100 children (46 peanut-allergic [PA] and 15 peanut-sensitized tolerant) who had Arah2-sIgE levels 0.10 kU/L or greater were studied. Arah2-sIgE and Ara h 6-specific IgE levels, Ara h 2/total IgE ratios, and the diversity of IgE for Ara h 2 epitopes were higher in PA compared with peanut-sensitized tolerant samples. The levels of IgE to peanut, Ara h 1, and Ara h 3 were not significantly different between groups. Results from the mast cell activation test to Ara h 2 strongly correlated with Arah2-sIgE levels (r = 0.722; P < .001) and Ara h 2/total IgE ratios (r = 0.697; P < .001) and moderately with Arah2-sIgE diversity (r = 0.540; P < .001). On a linear regression model, Arah2-sIgE levels (standardized β-coefficient = 0.396; P = .008) and Ara h 2/total IgE ratios (standardized β-coefficient = 0.0.669; P = .002) were the main determinants of mast cell response to Ara h 2. Conclusions: Most children sensitized to Ara h 2 are PA. Ara h 2-specific IgE titers and specific activity are the major determinants of mast cell response to Ara h 2.

AB - Background: Ara h 2-specific IgE (Arah2-sIgE) is an excellent serologic marker for peanut allergy. However, not all subjects with detectable Arah2-sIgE react clinically. Objective: To assess the importance of functional characteristics of Arah2-sIgE for Ara h 2-induced mast cell activation. Methods: We studied a cohort of children assessed for peanut allergy. We determined Arah2-sIgE levels, Ara h 2/total IgE ratios and IgE avidity for Ara h 2 using ImmunoCAP (Thermo Fisher) and mast cell activation to Ara h 2 using flow cytometry. Results: Samples from 61 of 100 children (46 peanut-allergic [PA] and 15 peanut-sensitized tolerant) who had Arah2-sIgE levels 0.10 kU/L or greater were studied. Arah2-sIgE and Ara h 6-specific IgE levels, Ara h 2/total IgE ratios, and the diversity of IgE for Ara h 2 epitopes were higher in PA compared with peanut-sensitized tolerant samples. The levels of IgE to peanut, Ara h 1, and Ara h 3 were not significantly different between groups. Results from the mast cell activation test to Ara h 2 strongly correlated with Arah2-sIgE levels (r = 0.722; P < .001) and Ara h 2/total IgE ratios (r = 0.697; P < .001) and moderately with Arah2-sIgE diversity (r = 0.540; P < .001). On a linear regression model, Arah2-sIgE levels (standardized β-coefficient = 0.396; P = .008) and Ara h 2/total IgE ratios (standardized β-coefficient = 0.0.669; P = .002) were the main determinants of mast cell response to Ara h 2. Conclusions: Most children sensitized to Ara h 2 are PA. Ara h 2-specific IgE titers and specific activity are the major determinants of mast cell response to Ara h 2.

KW - Anaphylaxis

KW - Ara h 2

KW - Food allergy

KW - IgE

KW - Mast cell activation

KW - Mast cells

KW - Peanut allergy

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U2 - 10.1016/j.jaip.2022.12.026

DO - 10.1016/j.jaip.2022.12.026

M3 - Article

C2 - 36581066

AN - SCOPUS:85147704697

SN - 2213-2198

VL - 11

SP - 1154-1161.e3

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

IS - 4

ER -

Ara h 2-Specific IgE Presence Rather Than Its Function Is the Best Predictor of Mast Cell Activation in Children

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