Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells - 26/09/24

Doi : 10.1016/j.jaci.2024.08.019

Craig I. McKenzie, PhD ^a, Simone Reinwald, PhD ^a,^b, Brett Averso, MSc ^c, Brett Spurrier, PhD ^c, Andrew Satz, MSc ^c, Anouk von Borstel, PhD ^a, Sabina Masinovic, MSc ^a, Nirupama Varese, MSc ^a,^b,^d, Pei Mun Aui, BSc ^a, Bruce D. Wines, PhD ^d, P. Mark Hogarth, PhD ^a,^d,^e, Mark Hew, FRACP, PhD ^b,^f, Jennifer M. Rolland, PhD ^a,^b, Robyn E. O’Hehir, FRACP, PhD ^a,^b, Menno C. van Zelm, PhD ^a,^b,^g,^⁎
^a Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Australia
^b Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, Australia
^c EVQLV, New York, NY
^d Immune Therapies Group, Burnet Institute, Melbourne, Australia
^e Department of Pathology, The University of Melbourne, Parkville, Australia
^f School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
^g Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

^∗Corresponding author: Menno C. van Zelm, PhD, Department of Immunology, Erasmus MC, Dr. Molewaterplein 40, Rotterdam, 3015GD, The Netherlands.Department of ImmunologyErasmus MCDr. Molewaterplein 40Rotterdam3015GDThe Netherlands

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Thursday 26 September 2024

Graphical abstract

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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.