Koppejan Hester, Smith Sophie-Anne I, Hameetman Marjolijn, Toes René E M, van Gaalen Floris A
Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2233 ZA, Leiden, The Netherlands.
Flow Cytometry Core Facility, Leiden University Medical Center, Leiden, The Netherlands.
Clin Rheumatol. 2025 Jan;44(1):495-502. doi: 10.1007/s10067-024-07233-7. Epub 2024 Nov 26.
Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are hallmarked by immune cell infiltration in synovial joints. Although, in general, different sites are affected, misclassification or delayed diagnosis due to overlapping clinical manifestations is not uncommon. Here, we investigated the diagnostic potential of mass cytometry (MC) in early peripheral SpA (pSpA) and RA patients in a small pilot study.
Peripheral blood and synovial fluid mononuclear cells (PBMC and SFMC) of 4 pSpA, 7 RA, and 1 undifferentiated arthritis (UA) patient(s) were evaluated using a 37-marker MC panel. Data were analyzed through Visualyte services, including dimension reduction, clustering, and Cytofast workflow.
PBMC data indicated naive CD4 T cell, B cell, and monocyte subsets to be differentially present in RA as compared with SpA. CD4 + Tem cell and NK cell subsets appeared more prominently present in pSpA SFMC. Merged PBMC and SFMC data showed overlapping immune profiles of an UA patient with pSpA patients. These results were in accordance with the formal clinical pSpA diagnosis the UA patient received after this study.
Utilizing MC, several differences in immune cell composition in both SFMC and PBMC between RA and pSpA patients were observed. Combining PBMC and SFMC data in an unsupervised analysis resulted in the correct classification of the UA patient as pSpA patient prior to formal clinical pSpA diagnosis. This pilot study provides an example of how deep phenotyping with MC aids in differentiating arthritis patients and offers a rationale to further explore these findings.
•Due to overlapping symptoms and the absence of disease-specific biomarkers, the clinical diagnosis of peripheral spondyloarthritis (pSpA) and rheumatoid arthritis (RA) can be difficult. •Visualizing immune cell profiles of peripheral blood (PB) and synovial fluid (SF) by mass cytometry (MC) suggests differences in immune cell composition between pSpA and RA patients. •Based on immune profiles of combined PB and SF data, we could correctly predict the formal clinical pSpA diagnosis of an undifferentiated arthritis (UA) patient received later. •This pilot study gives an example of how MC might contribute to faster clinical diagnosis of pSpA patients in the absence of biomarkers.
脊柱关节炎（SpA）和类风湿关节炎（RA）的特征是滑膜关节中有免疫细胞浸润。尽管一般来说受累部位不同，但由于临床表现重叠导致的误诊或诊断延迟并不少见。在此，我们在一项小型试点研究中调查了质谱流式细胞术（MC）在早期外周型SpA（pSpA）和RA患者中的诊断潜力。
使用一个包含37种标志物的MC检测板对4例pSpA、7例RA和1例未分化关节炎（UA）患者的外周血和滑膜液单核细胞（PBMC和SFMC）进行评估。数据通过Visualyte服务进行分析，包括降维、聚类和Cytofast工作流程。
PBMC数据表明，与SpA相比，RA中幼稚CD4 T细胞、B细胞和单核细胞亚群存在差异。CD4+Tem细胞和NK细胞亚群在pSpA的SFMC中更为突出。合并的PBMC和SFMC数据显示，一名UA患者与pSpA患者的免疫图谱存在重叠。这些结果与该UA患者在本研究后接受的正式临床pSpA诊断一致。
利用MC，观察到RA和pSpA患者的SFMC和PBMC中免疫细胞组成存在若干差异。在无监督分析中合并PBMC和SFMC数据，使得在正式临床pSpA诊断之前，该UA患者被正确分类为pSpA患者。这项试点研究提供了一个例子，说明MC深度表型分析如何有助于区分关节炎患者，并为进一步探索这些发现提供了理论依据。
•由于症状重叠且缺乏疾病特异性生物标志物，外周型脊柱关节炎（pSpA）和类风湿关节炎（RA）的临床诊断可能具有挑战性。•通过质谱流式细胞术（MC）观察外周血（PB）和滑膜液（SF）的免疫细胞图谱，提示pSpA和RA患者的免疫细胞组成存在差异。•基于合并的PB和SF数据的免疫图谱，我们能够正确预测一名未分化关节炎（UA）患者后来接受的正式临床pSpA诊断。•这项试点研究给出了一个例子，说明在缺乏生物标志物的情况下，MC如何可能有助于更快地对pSpA患者进行临床诊断。
