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
Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Australia.
Department of Immunology, School of Translational Medicine, Monash University, Melbourne, Australia; Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, Australia.
J Allergy Clin Immunol. 2024 Dec;154(6):1511-1522. doi: 10.1016/j.jaci.2024.08.019. Epub 2024 Aug 30.
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 IgG and IgG 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.
变应原免疫疗法（AIT）是唯一可改变过敏性疾病病情的治疗方法。我们最近发现，对于黑麦草花粉过敏，经过4个月的舌下AIT后，变应原特异性记忆B细胞（Bmem）的表型发生了改变。这些效应是否与皮下变应原免疫疗法（SCIT）相同，以及是否会影响Bmem的表位特异性，目前尚不清楚。
本研究旨在评估蜂毒（BV）过敏患者在接受超快速SCIT治疗前后，针对主要蜂毒变应原Api m 1的Bmem的表型和抗原受体序列。
制备重组Api m 1蛋白四聚体，以评估一组BV过敏患者在接受BV SCIT治疗前后的嗜碱性粒细胞活化情况。采用综合流式细胞术评估和纯化Api m 1特异性Bmem。对单个Api m 1特异性Bmem的免疫球蛋白基因进行测序，并在Api m 1上进行结构建模。
SCIT促进了Api m 1特异性Bmem向IgG和IgG的类别转换，同时CD23和CD29的表达增加。此外，对Bmem来源的Api m 1特异性免疫球蛋白进行建模，确定了Api m 1上一组可能的新的和多样的变应原表位，并突出显示了SCIT后可能优先与免疫球蛋白结合的表位。
AIT可诱导变应原特异性Bmem的表位特异性转移和表型变化。
