Hansen Bérénice, Da Costa Raul, Revets Dominique, Hedin Fanny, Konstantinou Maria, Jubal Eduardo Rosales, Ngangom Franck, Laczny Cédric C, Roomp Kirsten, Petrov Viacheslav, Michalsen Andreas, Hanslian Etienne, Koppold Daniela A, Khokhar Anika Rajput, Steckhan Nico, Jeitler Michael, Mollenhauer Brit, Schade Sebastian, Vaillant Michel, Cosma Antonio, Wilmes Paul, Schneider Jochen G
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Department of Translational Medicine Operations Hub (TMOH), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.
Mediators Inflamm. 2025 Jul 29;2025:9675331. doi: 10.1155/mi/9675331. eCollection 2025.
Over the past decades, the prevalence of noncommunicable diseases has surged significantly, including the systemic autoimmune disorder rheumatoid arthritis (RA). Despite extensive research and advancement of RA therapy, effective prevention strategies or cures remain elusive, and the mechanisms underlying RA pathogenesis unclear. It is crucial to gain deeper insights into RA pathophysiology. The objective of this study is to provide a comprehensive immunophenotyping of patients with RA. We generated and analyzed deep immunophenotyping data from 52 patients with RA and 47 healthy controls (HCs). Whole blood samples were stained with extracellular markers, and intracellular antibodies and analyzed for 32 different cell markers using mass cytometry by time of flight. The acquired data was analyzed by both manual and automatic unsupervised tools and subsequently complemented with anthropometric data and clinical-laboratory parameters. We observed a significant disparity in immune cell profiles between patients with RA and HC, notably a reduced frequency of CD27IgD unswitched memory B (B) cells in patients with RA (-value < 0.01), with the disease RA being the primary and only significant factor explaining up to 17.9% of the variance of these cells. Our results reveal, for the first time, that a reduced frequency of unswitched B cells in patients with RA is the only significant abnormality distinguishing patients with RA from HC in a complex immunophenotyping panel of 72 different cell populations. This provides important information to further individualize various interventions and possibly help to design novel therapeutic interventions.
在过去几十年中，包括系统性自身免疫性疾病类风湿关节炎（RA）在内的非传染性疾病患病率显著飙升。尽管对RA治疗进行了广泛研究并取得了进展，但有效的预防策略或治愈方法仍然难以捉摸，RA发病机制背后的原因也尚不清楚。深入了解RA病理生理学至关重要。本研究的目的是对RA患者进行全面的免疫表型分析。我们生成并分析了52例RA患者和47例健康对照（HC）的深度免疫表型数据。全血样本用细胞外标志物和细胞内抗体进行染色，并使用飞行时间质谱流式细胞术分析32种不同的细胞标志物。通过手动和自动无监督工具对获取的数据进行分析，随后补充人体测量数据和临床实验室参数。我们观察到RA患者和HC之间的免疫细胞谱存在显著差异，特别是RA患者中CD27IgD未转换记忆B（B）细胞的频率降低（P值<0.01），RA疾病是解释这些细胞变异高达17.9%的主要且唯一显著因素。我们的结果首次揭示，在一个由72种不同细胞群体组成的复杂免疫表型分析中，RA患者未转换B细胞频率降低是将RA患者与HC区分开来的唯一显著异常。这为进一步个性化各种干预措施提供了重要信息，并可能有助于设计新的治疗干预措施。
