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Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells

[Display omitted] Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B cells (Bmem) are phenotypically altered after 4 months of sublingual AIT for ryegrass pollen allergy. Whether these effects are s...

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Published in:Journal of allergy and clinical immunology 2024-12, Vol.154 (6), p.1511-1522
Main Authors: McKenzie, Craig I., Reinwald, Simone, Averso, Brett, Spurrier, Brett, Satz, Andrew, von Borstel, Anouk, Masinovic, Sabina, Varese, Nirupama, Aui, Pei Mun, Wines, Bruce D., Hogarth, P. Mark, Hew, Mark, Rolland, Jennifer M., O’Hehir, Robyn E., van Zelm, Menno C.
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container_end_page 1522
container_issue 6
container_start_page 1511
container_title Journal of allergy and clinical immunology
container_volume 154
creator McKenzie, Craig I.
Reinwald, Simone
Averso, Brett
Spurrier, Brett
Satz, Andrew
von Borstel, Anouk
Masinovic, Sabina
Varese, Nirupama
Aui, Pei Mun
Wines, Bruce D.
Hogarth, P. Mark
Hew, Mark
Rolland, Jennifer M.
O’Hehir, Robyn E.
van Zelm, Menno C.
description [Display omitted] Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B cells (Bmem) are phenotypically altered after 4 months of sublingual AIT for ryegrass pollen allergy. Whether these effects are shared with subcutaneous allergen immunotherapy (SCIT) and affect the epitope specificity of Bmem remain unknown. The study aimed to evaluate the phenotype and antigen receptor sequences of Bmem specific to the major bee venom (BV) allergen Api m 1 before and after ultra-rush SCIT for BV allergy. Recombinant Api m 1 protein tetramers were generated to evaluate basophil activation in a cohort of individuals with BV allergy before and after BV SCIT. Comprehensive flow cytometry was performed to evaluate and purify Api m 1–specific Bmem. Immunoglobulin genes from single Api m 1–specific Bmem were sequenced and structurally modeled onto Api m 1. SCIT promoted class switching of Api m 1–specific Bmem to IgG2 and IgG4 with increased expression of CD23 and CD29. Furthermore, modeling of Api m 1–specific immunoglobulin from Bmem identified a suite of possible new and diverse allergen epitopes on Api m 1 and highlighted epitopes that may preferentially be bound by immunoglobulin after SCIT. AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.
doi_str_mv 10.1016/j.jaci.2024.08.019
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Mark ; Hew, Mark ; Rolland, Jennifer M. ; O’Hehir, Robyn E. ; van Zelm, Menno C.</creator><creatorcontrib>McKenzie, Craig I. ; Reinwald, Simone ; Averso, Brett ; Spurrier, Brett ; Satz, Andrew ; von Borstel, Anouk ; Masinovic, Sabina ; Varese, Nirupama ; Aui, Pei Mun ; Wines, Bruce D. ; Hogarth, P. Mark ; Hew, Mark ; Rolland, Jennifer M. ; O’Hehir, Robyn E. ; van Zelm, Menno C.</creatorcontrib><description>[Display omitted] Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B cells (Bmem) are phenotypically altered after 4 months of sublingual AIT for ryegrass pollen allergy. Whether these effects are shared with subcutaneous allergen immunotherapy (SCIT) and affect the epitope specificity of Bmem remain unknown. The study aimed to evaluate the phenotype and antigen receptor sequences of Bmem specific to the major bee venom (BV) allergen Api m 1 before and after ultra-rush SCIT for BV allergy. Recombinant Api m 1 protein tetramers were generated to evaluate basophil activation in a cohort of individuals with BV allergy before and after BV SCIT. Comprehensive flow cytometry was performed to evaluate and purify Api m 1–specific Bmem. Immunoglobulin genes from single Api m 1–specific Bmem were sequenced and structurally modeled onto Api m 1. SCIT promoted class switching of Api m 1–specific Bmem to IgG2 and IgG4 with increased expression of CD23 and CD29. Furthermore, modeling of Api m 1–specific immunoglobulin from Bmem identified a suite of possible new and diverse allergen epitopes on Api m 1 and highlighted epitopes that may preferentially be bound by immunoglobulin after SCIT. 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subjects Adult
allergen epitopes
allergen-specific
Allergens - immunology
Animals
Bee Venoms - immunology
Desensitization, Immunologic - methods
Epitopes - immunology
Epitopes, B-Lymphocyte - immunology
Female
Humans
Hypersensitivity - immunology
Hypersensitivity - therapy
Immunophenotyping
Immunotherapy
Injections, Subcutaneous
Insect Proteins - immunology
Male
memory B cells
Memory B Cells - immunology
Middle Aged
Phospholipases A
Venom Hypersensitivity
title Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells
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