Dept of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany.
Eur Respir J. 2022 Nov 3;60(5). doi: 10.1183/13993003.02130-2021. Print 2022 Nov.
Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.
In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models.
Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgA memory B-cells were associated with impaired lung function and specifically with parameters indicative for augmented resistance in the peripheral airways. Accordingly, asthma patients with small airway dysfunction (SAD) defined by impulse oscillometry showed increased frequencies of IgA memory B-cells, particularly in patients with mild-moderate asthma. Additionally, IgA memory B-cells significantly correlated with clinical features of SAD such as exacerbations.
With this study we demonstrate for the first time a significant association of increased IgA memory B-cells with asthma and SAD, pointing towards future options for B-cell-directed strategies in preventing and treating asthma.
全面研究了 T 细胞在哮喘中的作用,这导致了针对严重嗜酸性粒细胞性哮喘的个体化治疗选择。然而,对于 B 细胞在这种慢性炎症性疾病中的作用知之甚少。在这项研究中,我们研究了各种 B 细胞群体对哮喘特定临床特征的贡献。
在全年龄段哮喘队列(ALLIANCE)中,纳入了 154 名成年哮喘患者和 28 名健康对照者,通过流式细胞术对 B 细胞进行特征分析。使用关联研究和多元线性模型,将参与者的问卷、肺功能测量、血液差异计数和过敏测试与 B 细胞的综合数据一起进行分析。
与轻度至中度哮喘患者和健康对照组相比,严重哮喘患者的幼稚 B 细胞群体减少,而记忆 B 细胞显著增加。此外,IgA 记忆 B 细胞的频率增加与肺功能受损有关,特别是与外周气道阻力增加的参数有关。因此,通过脉冲振荡测量定义的小气道功能障碍(SAD)的哮喘患者,IgA 记忆 B 细胞的频率增加,特别是在轻度至中度哮喘患者中。此外,IgA 记忆 B 细胞与 SAD 的临床特征显著相关,如恶化。
通过这项研究,我们首次证明 IgA 记忆 B 细胞与哮喘和 SAD 显著相关,这为未来预防和治疗哮喘的 B 细胞靶向策略提供了新的选择。