Exosomal microRNAs in Different Disease Activity Status in Systemic Lupus Erythematosus: A Retrospective Study.

IF 1.1 Q4 RHEUMATOLOGY
Wenyu Xu, Peiying Nie, Qian Li, Bingjie Gu, Qijie Ren, Xingguo Chen
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Abstract

Background/Aims: Differential miRNA expression profiles in the plasma exosomes of systemic lupus erythematosus (SLE) patients were obtained at various disease activity stages and compared with healthy controls. Materials and Methods: Plasma samples were collected from 48 SLE patients with high, medium, and low disease activity and from 20 healthy controls. The sample set was retrospectively analyzed for differences in clinical features. Plasma exosomes were extracted and subjected to comprehensive detection and analysis. Total exosomal RNA was extracted from the 4 groups, and differential expression profiles were analyzed using miRNA chip technology. Results: Significant differences in clinical parameters-including platelet count (PLT), erythrocyte sedimentation rate (ESR), 24-hour urinary protein, and complement C3/C4 levels-were observed among SLE patients with different disease activity levels (all P < .05). Plasma exosomes were successfully isolated and characterized. Microarray analysis identified distinct exosomal miRNA profiles. Notably, let-7a-5p and miR-23a-3p were significantly downregulated in patients with high disease activity compared to those with low activity (fold change > 2, P < .0001), while miR-4532 was markedly upregulated. Correlation analysis showed let-7a-5p expression was positively associated with PLT (r = 0.61) and complement C3 (r = 0.69) and negatively with ESR (r = -0.65). Conversely, miR-4532 was positively correlated with ESR (r = 0.67) and urinary protein (r = 0.56) and negatively with C3 and C4 (both r = -0.67). Conclusion: Differential miRNA expression was identified in the exosomes of SLE patients at various disease activity levels. These findings indicate the crucial role of these miRNAs in the onset and progression of SLE, providing a basis for further investigation of the immunoregulatory functions of exosomes.

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系统性红斑狼疮不同疾病活动状态外泌体microRNAs的回顾性研究
背景/目的:研究了系统性红斑狼疮(SLE)患者在不同疾病活动期血浆外泌体中miRNA的差异表达谱,并与健康对照进行了比较。材料与方法:收集48例SLE高、中、低疾病活动度患者和20例健康对照者的血浆样本。回顾性分析样本组的临床特征差异。提取血浆外泌体并进行综合检测和分析。提取4组总外泌体RNA,采用miRNA芯片技术分析差异表达谱。结果:不同疾病活动度SLE患者血小板计数(PLT)、红细胞沉降率(ESR)、24小时尿蛋白、补体C3/C4水平等临床指标差异有统计学意义(均P < 0.05)。成功分离并鉴定了血浆外泌体。微阵列分析鉴定出不同的外泌体miRNA谱。值得注意的是,与低活动性患者相比,let-7a-5p和miR-23a-3p在疾病活动性高的患者中显著下调(fold change >2, P < 0.0001),而miR-4532则显著上调。相关分析显示let-7a-5p表达与PLT (r = 0.61)、补体C3 (r = 0.69)呈正相关,与ESR呈负相关(r = -0.65)。相反,miR-4532与ESR (r = 0.67)和尿蛋白(r = 0.56)呈正相关,与C3和C4呈负相关(r = -0.67)。结论:在不同疾病活动水平的SLE患者外泌体中发现了差异miRNA表达。这些发现表明这些mirna在SLE的发生和发展中起着至关重要的作用,为进一步研究外泌体的免疫调节功能提供了基础。
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