Circulating B Cells Display Differential Immune Regulatory Molecule Expression in Granulomatosis with Polyangiitis.

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Carlo G Bonasia, Nanthicha Inrueangsri, Theo Bijma, Malte Borggrewe, Aline I Post, Kevin P Mennega, Wayel H Abdulahad, Abraham Rutgers, Nicolaas A Bos, Peter Heeringa
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Abstract

Granulomatosis with polyangiitis (GPA) is a B cell-mediated, relapsing, autoimmune disease. There is a need for novel therapeutic approaches and relapse markers to achieve durable remission. B cells express immune regulatory molecules that modulate their activation and maintain tolerance. While recent studies show dysregulation of these molecules in other autoimmune diseases, data on their expression in GPA are limited. This study aimed to map the expression of surface immune regulatory molecules on circulating B cell subsets in GPA and correlate their expression with clinical parameters. Immune regulatory molecule expression on circulating B cell subsets was comprehensively examined in active GPA (n=16), GPA in remission (n=16), and healthy controls (HCs, n=16) cross-sectionally using a 35-color B cell-specific spectral flow cytometry panel. Our supervised and unsupervised in-depth analysis revealed differential expression of inhibitory and stimulatory immune molecules on distinct B cell populations in GPA, with the most notable differences observed in active GPA. These differences include the upregulation of FcγRIIB on non-mature B cells, downregulation of CD21 and upregulation of CD86 on antigen-experienced B cells, and elevated CD22 expression on various populations. Additionally, we found a strong association between FcγRIIB, BTLA, and CD21 expression on specific B cell populations and disease activity in GPA. Together, these findings provide novel insights into the immune regulatory molecule expression profile of B cells in GPA, and could potentially form the foundation for new therapeutic approaches and disease monitoring markers.

肉芽肿性多血管炎患者循环 B 细胞的免疫调节分子表达存在差异
多血管炎肉芽肿病(GPA)是一种由 B 细胞介导的复发性自身免疫性疾病。目前需要新的治疗方法和复发标志物来实现持久缓解。B 细胞表达的免疫调节分子可调节其活化并维持耐受性。虽然最近的研究显示这些分子在其他自身免疫性疾病中的表达失调,但有关它们在 GPA 中表达的数据却很有限。本研究旨在绘制 GPA 循环 B 细胞亚群表面免疫调节分子的表达图,并将其表达与临床参数相关联。我们使用 35 色 B 细胞特异性光谱流式细胞仪面板,全面检测了活动期 GPA(16 人)、缓解期 GPA(16 人)和健康对照组(16 人)中循环 B 细胞亚群上免疫调节分子的表达。我们的有监督和无监督深入分析显示,GPA 中不同的 B 细胞群中抑制性和刺激性免疫分子的表达存在差异,在活动期 GPA 中观察到的差异最为显著。这些差异包括非成熟 B 细胞上 FcγRIIB 的上调、抗原经验丰富的 B 细胞上 CD21 的下调和 CD86 的上调,以及各种细胞群中 CD22 表达的升高。此外,我们还发现特定 B 细胞群的 FcγRIIB、BTLA 和 CD21 表达与 GPA 的疾病活动性之间存在密切联系。这些发现为了解 GPA 中 B 细胞的免疫调节分子表达谱提供了新的视角,有可能为新的治疗方法和疾病监测标记物奠定基础。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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