Endothelial progenitor cells (EPCs) are essential for maintenance of vascular homeostasis and stability, key processes in the pathogenesis of systemic lupus erythematosus (SLE). However, the role and phenotypic characterization of EPCs populations in SLE have not been completely elucidated. To identify EPCs specific subpopulations in patients with SLE using a novel flow cytometry tool. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SLE and healthy controls (HC). mRNA and surface protein expression were determined by quantitative PCR (qPCR) and flow cytometry. Clusters identification and characterization were performed using tSNE-CUDA dimensionality reduction algorithms. tSNE-CUDA analysis identified eight different clusters in PBMCs from HC and patients with SLE. Three of these clusters had EPC-like phenotype and the expression was elevated in patients with SLE. Moreover, four SLE-associated subclusters were found mainly expressed in patients with SLE, being only present in patients in remission with SLE and significantly associated with the 2021 Definition of Remission in SLE. Importantly, we also identified specific clusters in SLE patients with organ damage, according to the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI). These clusters showed an EPC-like phenotype, but the expression of angiogenic markers was lower compared to HC or patients without organ damage, suggesting an impaired angiogenic function. Our novel approach identified clusters of EPCs in patients with SLE that are associated with remission and damage. Therefore, these clusters might be useful biomarkers to predict disease progression and severity in SLE pathogenesis.

中文翻译：

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新型内皮祖细胞群作为系统性红斑狼疮损伤和缓解的生物标志物


内皮祖细胞 (EPC) 对于维持血管稳态和稳定性至关重要，这是系统性红斑狼疮 (SLE) 发病机制的关键过程。然而，EPCs 群体在 SLE 中的作用和表型特征尚未完全阐明。使用新型流式细胞术工具识别 SLE 患者的 EPC 特异性亚群。从 SLE 患者和健康对照 (HC) 中分离外周血单核细胞 (PBMC)。通过定量 PCR (qPCR) 和流式细胞术测定 mRNA 和表面蛋白表达。使用 tSNE-CUDA 降维算法进行簇识别和表征。 tSNE-CUDA 分析确定了来自 HC 和 SLE 患者的 PBMC 中的八个不同簇。其中三个簇具有 EPC 样表型，并且在 SLE 患者中表达升高。此外，发现四个与 SLE 相关的亚群主要在 SLE 患者中表达，仅存在于 SLE 缓解患者中，并且与 2021 年 SLE 缓解定义显着相关。重要的是，根据系统性狼疮国际合作诊所 (SLICC)/美国风湿病学会损伤指数 (SDI)，我们还确定了 SLE 患者器官损伤的特定集群。这些簇表现出类似 EPC 的表型，但与 HC 或无器官损伤的患者相比，血管生成标志物的表达较低，表明血管生成功能受损。我们的新方法确定了 SLE 患者中与缓解和损害相关的 EPC 簇。因此，这些簇可能是预测 SLE 发病机制中疾病进展和严重程度的有用生物标志物。