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

Craig I. McKenzie; Simone Reinwald; Brett Averso; Brett Spurrier; Andrew Satz; Anouk von Borstel; Sabina Masinovic; Nirupama Varese; Pei Mun Aui; Bruce D. Wines; P. Mark Hogarth; Mark Hew; Jennifer M. Rolland; Robyn E. O'Hehir; Menno C. van Zelm

doi:10.1016/j.jaci.2024.08.019

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

Craig I. McKenzie, Simone Reinwald, Brett Averso, Brett Spurrier, Andrew Satz, Anouk von Borstel, Sabina Masinovic, Nirupama Varese, Pei Mun Aui, Bruce D. Wines, P. Mark Hogarth, Mark Hew, Jennifer M. Rolland, Robyn E. O'Hehir, Menno C. van Zelm^*

^*Corresponding author for this work

Immunology

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

3 Citations (Scopus)

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Abstract

Background:

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.

Objective:

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. Methods: 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.

Results:

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.

Conclusions:

AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.

Original language	English
Pages (from-to)	1511-1522
Number of pages	12
Journal	Journal of Allergy and Clinical Immunology
Volume	154
Issue number	6
DOIs	https://doi.org/10.1016/j.jaci.2024.08.019
Publication status	Published - Dec 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

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10.1016/j.jaci.2024.08.019Licence: CC BY

Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cellsFinal published version, 4.66 MBLicence: CC BY

Cite this

McKenzie, C. I., Reinwald, S., Averso, B., Spurrier, B., Satz, A., von Borstel, A., Masinovic, S., Varese, N., Aui, P. M., Wines, B. D., Hogarth, P. M., Hew, M., Rolland, J. M., O'Hehir, R. E., & van Zelm, M. C. (2024). Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells. Journal of Allergy and Clinical Immunology, 154(6), 1511-1522. https://doi.org/10.1016/j.jaci.2024.08.019

@article{64bb373af0b844938d4ceb26a9ebc2d1,

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

abstract = "Background: 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.Objective: 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. Methods: 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. Results: 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. Conclusions: AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.",

author = "McKenzie, {Craig I.} and Simone Reinwald and Brett Averso and Brett Spurrier and Andrew Satz and {von Borstel}, Anouk and Sabina Masinovic and Nirupama Varese and Aui, {Pei Mun} and Wines, {Bruce D.} and Hogarth, {P. Mark} and Mark Hew and Rolland, {Jennifer M.} and O'Hehir, {Robyn E.} and {van Zelm}, {Menno C.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = dec,

doi = "10.1016/j.jaci.2024.08.019",

language = "English",

volume = "154",

pages = "1511--1522",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "6",

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McKenzie, CI, Reinwald, S, Averso, B, Spurrier, B, Satz, A, von Borstel, A, Masinovic, S, Varese, N, Aui, PM, Wines, BD, Hogarth, PM, Hew, M, Rolland, JM, O'Hehir, RE & van Zelm, MC 2024, 'Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells', Journal of Allergy and Clinical Immunology, vol. 154, no. 6, pp. 1511-1522. https://doi.org/10.1016/j.jaci.2024.08.019

Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells. / McKenzie, Craig I.; Reinwald, Simone; Averso, Brett et al.
In: Journal of Allergy and Clinical Immunology, Vol. 154, No. 6, 12.2024, p. 1511-1522.

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

TY - JOUR

T1 - Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells

AU - McKenzie, Craig I.

AU - Reinwald, Simone

AU - Averso, Brett

AU - Spurrier, Brett

AU - Satz, Andrew

AU - von Borstel, Anouk

AU - Masinovic, Sabina

AU - Varese, Nirupama

AU - Aui, Pei Mun

AU - Wines, Bruce D.

AU - Hogarth, P. Mark

AU - Hew, Mark

AU - Rolland, Jennifer M.

AU - O'Hehir, Robyn E.

AU - van Zelm, Menno C.

PY - 2024/12

Y1 - 2024/12

N2 - Background: 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.Objective: 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. Methods: 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. Results: 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. Conclusions: AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.

AB - Background: 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.Objective: 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. Methods: 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. Results: 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. Conclusions: AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.

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U2 - 10.1016/j.jaci.2024.08.019

DO - 10.1016/j.jaci.2024.08.019

M3 - Article

C2 - 39218358

AN - SCOPUS:85203840878

SN - 0091-6749

VL - 154

SP - 1511

EP - 1522

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 6

ER -

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

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