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
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引用次数: 0
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.
背景：过敏原免疫疗法（AIT过敏原免疫疗法（AIT）是治疗过敏性疾病的唯一疾病改变疗法。我们最近发现，经过 4 个月的舌下 AIT 治疗黑麦草花粉过敏后，过敏原特异性记忆 B 细胞（Bmem）的表型发生了改变。这些影响是否与皮下注射 AIT（SCIT）相同并影响 Bmem 的表位特异性仍是未知数：目的：评估 Bmem 在超急速 SCIT 治疗 BV 过敏症前后对主要蜂毒（BV）过敏原 Api m 1 特异性的表型和抗原受体序列：方法：生成重组 Api m 1 蛋白四聚体，以评估 BV SCIT 前后一组 BV 过敏个体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 Ig 基因进行了测序，并对 Api m 1 进行了结构建模：结果：SCIT促进了Api m 1特异性Bmem向IgG2和IgG4的类别转换，并增加了CD23和CD29的表达。此外，通过对 Bmem 的 Api m 1 特异性 Ig 建模，发现了 Api m 1 上可能存在的一系列新的、多样的过敏原表位，并强调了 SCIT 后 Ig 可能优先结合的表位：结论：AIT 会诱导过敏原特异性 Bmem 表位特异性的转变和表型的改变。
期刊介绍：
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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