Universidad de Antioquia Grupo de Inmunología Celular e Inmunogenética, Medellin, Colombia.
Grupo de Reumatología, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia.
Lupus Sci Med. 2024 Aug 17;11(2):e001243. doi: 10.1136/lupus-2024-001243.
This study aimed to identify the physicochemical and phenotypic characteristics of circulating Extracellular Vesicles (EVs) in the plasma of patients with SLE, with or without Lupus Nephritis (LN), and their potential utility as disease biomarkers.
Plasma-circulating EVs were concentrated using differential centrifugation from adult female patients (n=38) who met the 'American College of Rheumatology/European Alliance of Associations for Rheumatology 2019' criteria for SLE diagnosis with (LN) or without LN (nLN), confirmed by renal biopsy. Controls (n=18) were healthy volunteers matched by gender and similar age. The structure, size and Energy Dispersion Spectrum (EDS) of EVs were observed by electron microscopy. The surface charge and size distribution were evaluated using dynamic light scattering. The counts and phenotype of EVs from patients (SLE-EVs) and controls (Ctrl-EVs) were obtained using flow cytometry. Non-parametric statistical tests and exploratory analysis of multiple variables were performed. The discriminatory power of some variables as potential biomarkers of the disease was also evaluated.
Circulating EVs were heterogeneous in morphology and size, but SLE-EVs reached larger diameters than Ctrl-EVs (p<0.0001). Small SLE-EVs and large SLE-EVs were increased compared with Ctrl-EV (p<0.0001 and p<0.05, respectively). Likewise, patients with SLE (LN or nLN) had higher concentrations of large EVs compared with controls (p<0.001 and p<0.0001, respectively). SLE-EVs showed a different EDS (p<0.001) and were less electronegative (p<0.0001) than Ctrl-EVs. EV-CD45+, EV-CD14+ and EV-IgM+ were more frequent in patients with SLE compared with controls (p<0.001, p<0.05 and p<0.001, respectively). The concentrations of large EVs and EV-IgM+ allowed better discrimination of patients from controls.
Plasma-circulating EVs from patients with SLE with and without nephritis are increased in peripheral blood and have different physicochemical properties than controls. Characteristics of EVs such as larger size and the presence of IgM on the surface could help discriminate patients from controls.
本研究旨在鉴定患有狼疮性肾炎（LN）或无 LN 的系统性红斑狼疮（SLE）患者血浆中循环细胞外囊泡（EVs）的理化和表型特征，及其作为疾病生物标志物的潜在用途。
使用差速离心法从符合 2019 年美国风湿病学会/欧洲抗风湿病联盟 SLE 诊断标准（伴有或不伴有 LN）的成年女性患者（n=38）的血浆中浓缩 EVs，LN 通过肾活检证实。对照组（n=18）为性别和年龄相匹配的健康志愿者。使用电子显微镜观察 EVs 的结构、大小和能量色散谱（EDS）。使用动态光散射评估表面电荷和粒径分布。使用流式细胞术获得患者（SLE-EVs）和对照组（Ctrl-EVs）的 EVs 计数和表型。进行非参数统计检验和多变量探索性分析。还评估了一些作为疾病潜在生物标志物的变量的区分能力。
循环 EVs 在形态和大小上具有异质性，但与 Ctrl-EVs 相比，SLE-EVs 的直径更大（p<0.0001）。与 Ctrl-EV 相比，小 SLE-EVs 和大 SLE-EVs 增加（p<0.0001 和 p<0.05）。同样，与对照组相比，患有 SLE（LN 或 nLN）的患者具有更高浓度的大 EVs（p<0.001 和 p<0.0001）。SLE-EVs 的 EDS 不同（p<0.001），且比 Ctrl-EVs 带负电荷更少（p<0.0001）。与对照组相比，SLE 患者的 EV-CD45+、EV-CD14+和 EV-IgM+更为常见（p<0.001、p<0.05 和 p<0.001）。大 EVs 和 EV-IgM+的浓度可以更好地区分患者和对照组。
患有 LN 或无 LN 的 SLE 患者的血浆循环 EVs 在周围血液中增加，并且具有与对照组不同的理化性质。EVs 的特征，如较大的尺寸和表面上存在 IgM，可能有助于区分患者和对照组。
