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Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy

BACKGROUND: 10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms. OBJECTIVE: We used novel, human, allergen-spec...

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Autores principales: Suber, Jada, Zhang, Yugen, Ye, Ping, Guo, Rishu, Burks, A. Wesley, Kulis, Michael D., Smith, Scott A., Iweala, Onyinye I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556733/
https://www.ncbi.nlm.nih.gov/pubmed/36248809
http://dx.doi.org/10.3389/fimmu.2022.974374
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author Suber, Jada
Zhang, Yugen
Ye, Ping
Guo, Rishu
Burks, A. Wesley
Kulis, Michael D.
Smith, Scott A.
Iweala, Onyinye I.
author_facet Suber, Jada
Zhang, Yugen
Ye, Ping
Guo, Rishu
Burks, A. Wesley
Kulis, Michael D.
Smith, Scott A.
Iweala, Onyinye I.
author_sort Suber, Jada
collection PubMed
description BACKGROUND: 10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms. OBJECTIVE: We used novel, human, allergen-specific, IgE monoclonal antibodies (mAbs) created using human hybridoma techniques to design an in vitro system to evaluate potential therapeutics targeting sensitized effector cells. METHODS: Two human IgE mAbs specific for peanut, generated through human hybridoma techniques, were used to sensitize rat basophilic leukemia (RBL) SX-38 cells expressing the human IgE receptor (FcϵRI). Beta-hexosaminidase release (a marker of degranulation), cytokine production, and phosphorylation of signal transduction proteins downstream of FcϵRI were measured after stimulation with peanut. Degranulation was also measured after engaging inhibitory receptors CD300a and Siglec-8. RESULTS: Peanut-specific human IgE mAbs bound FcϵRI, triggering degranulation after stimulation with peanut in RBL SX-38 cells. Sensitized RBL SX-38 cells stimulated with peanut increased levels of phosphorylated SYK and ERK, signal transduction proteins downstream of FcϵRI. Engaging inhibitory cell surface receptors CD300a or Siglec-8 blunted peanut-specific activation. CONCLUSION: Allergen-specific human IgE mAbs, expressed from human hybridomas and specific for a clinically relevant food allergen, passively sensitize allergy effector cells central to the in vitro models of the effector phase of food allergy. Peanut reproducibly activates and induces degranulation of RBL SX-38 cells sensitized with peanut-specific human IgE mAbs. This system provides a unique screening tool to assess the efficacy of therapeutics that target allergy effector cells and inhibit food allergen-induced effector cell activation.
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spelling pubmed-95567332022-10-14 Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy Suber, Jada Zhang, Yugen Ye, Ping Guo, Rishu Burks, A. Wesley Kulis, Michael D. Smith, Scott A. Iweala, Onyinye I. Front Immunol Immunology BACKGROUND: 10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms. OBJECTIVE: We used novel, human, allergen-specific, IgE monoclonal antibodies (mAbs) created using human hybridoma techniques to design an in vitro system to evaluate potential therapeutics targeting sensitized effector cells. METHODS: Two human IgE mAbs specific for peanut, generated through human hybridoma techniques, were used to sensitize rat basophilic leukemia (RBL) SX-38 cells expressing the human IgE receptor (FcϵRI). Beta-hexosaminidase release (a marker of degranulation), cytokine production, and phosphorylation of signal transduction proteins downstream of FcϵRI were measured after stimulation with peanut. Degranulation was also measured after engaging inhibitory receptors CD300a and Siglec-8. RESULTS: Peanut-specific human IgE mAbs bound FcϵRI, triggering degranulation after stimulation with peanut in RBL SX-38 cells. Sensitized RBL SX-38 cells stimulated with peanut increased levels of phosphorylated SYK and ERK, signal transduction proteins downstream of FcϵRI. Engaging inhibitory cell surface receptors CD300a or Siglec-8 blunted peanut-specific activation. CONCLUSION: Allergen-specific human IgE mAbs, expressed from human hybridomas and specific for a clinically relevant food allergen, passively sensitize allergy effector cells central to the in vitro models of the effector phase of food allergy. Peanut reproducibly activates and induces degranulation of RBL SX-38 cells sensitized with peanut-specific human IgE mAbs. This system provides a unique screening tool to assess the efficacy of therapeutics that target allergy effector cells and inhibit food allergen-induced effector cell activation. Frontiers Media S.A. 2022-09-29 /pmc/articles/PMC9556733/ /pubmed/36248809 http://dx.doi.org/10.3389/fimmu.2022.974374 Text en Copyright © 2022 Suber, Zhang, Ye, Guo, Burks, Kulis, Smith and Iweala https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Suber, Jada
Zhang, Yugen
Ye, Ping
Guo, Rishu
Burks, A. Wesley
Kulis, Michael D.
Smith, Scott A.
Iweala, Onyinye I.
Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
title Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
title_full Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
title_fullStr Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
title_full_unstemmed Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
title_short Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
title_sort novel peanut-specific human ige monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556733/
https://www.ncbi.nlm.nih.gov/pubmed/36248809
http://dx.doi.org/10.3389/fimmu.2022.974374
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