Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Front Immunol. 2024 Oct 11;15:1449296. doi: 10.3389/fimmu.2024.1449296. eCollection 2024.
Lupus nephritis (LN) is one of the most prevalent severe organ manifestations of systemic lupus erythematosus (SLE), impacting 70% of SLE patients. MicroRNAs (miRNAs), are small non-coding RNA molecules which influence the expression of approximately one-third of human genes after the process of transcription. Dysregulation of miRNAs was documented in numerous disorders, including SLE and LN. Cytokines are the orchestrators of the immune response in autoimmune diseases. Our study aims to explore the variation in the levels of circulating miRNAs and proinflammatory cytokines as potential diagnostic biomarkers among LN and SLE patients without LN in comparison to controls.
The study involved 20 LN patients, 20 SLE patients without LN, and 10 healthy controls. Serum levels of IL-12 and IL-21 in addition to miR-124, miR-146a, miR-199a, and miR-21 were assessed using the enzyme-linked immunosorbent assay (ELISA) for cytokines and quantitative real-time PCR for miRNAs.
A significant downregulation in miR-124 (p<0.001) and a significant overexpression of miR-146a (p=0.005) were found in SLE patients without LN in comparison to controls. In comparison to SLE patients without LN and the control group, miR-199a, miR-21, and miR-146a were significantly upregulated in LN patients (p=<0.001) with high diagnostic values of these miRNAs in discriminating LN from SLE patients without LN according to Receiver operating curve (ROC) analysis. Logistic regression analysis revealed that only miR-199a is an independent predictor of LN (OR 1.69; 95% CI: 1.1-2.6). The expression of miR-124 was reduced in LN patients in comparison to the control but increased in LN patients in comparison to SLE patients without LN. However, there was no statistically significant difference in either scenario. In comparison to both SLE patients without LN and controls, LN patients exhibited the highest serum levels of IL-12 and IL-21, with no statistically significant difference. Regression analysis revealed that only miR-146a was associated with creatinine levels and SLEDAI score (p= 0.009 and 0.03, respectively), while miR-124 was associated with hemoglobin level (p=0.03).
MiR-199a is an independent predictor for LN and might be used as a diagnostic biomarker for this disease. MiR-146a might play an important role in LN pathophysiology.
狼疮肾炎（LN）是系统性红斑狼疮（SLE）最常见的严重器官表现之一，影响 70%的 SLE 患者。微小 RNA（miRNA）是小的非编码 RNA 分子，在转录后可影响约三分之一的人类基因的表达。miRNA 的失调已在许多疾病中得到证实，包括 SLE 和 LN。细胞因子是自身免疫性疾病中免疫反应的协调者。我们的研究旨在探讨 LN 和无 LN 的 SLE 患者与对照组相比，循环 miRNA 和促炎细胞因子水平的变化是否可作为潜在的诊断生物标志物。
本研究纳入了 20 例 LN 患者、20 例无 LN 的 SLE 患者和 10 例健康对照。采用酶联免疫吸附试验（ELISA）检测细胞因子，采用定量实时 PCR 检测 miRNA，评估血清中白细胞介素-12（IL-12）和白细胞介素-21（IL-21）以及 miR-124、miR-146a、miR-199a 和 miR-21 的水平。
与对照组相比，无 LN 的 SLE 患者的 miR-124 显著下调（p<0.001），miR-146a 显著上调（p=0.005）。与无 LN 的 SLE 患者和对照组相比，LN 患者的 miR-199a、miR-21 和 miR-146a 显著上调（p<0.001），根据受试者工作特征（ROC）曲线分析，这些 miRNA 对区分 LN 与无 LN 的 SLE 患者具有较高的诊断价值。Logistic 回归分析显示，只有 miR-199a 是 LN 的独立预测因子（OR 1.69；95%CI：1.1-2.6）。与对照组相比，LN 患者的 miR-124 表达降低，但与无 LN 的 SLE 患者相比，其表达增加。然而，两种情况下均无统计学差异。与无 LN 的 SLE 患者和对照组相比，LN 患者的血清 IL-12 和 IL-21 水平最高，但无统计学差异。回归分析显示，只有 miR-146a 与肌酐水平和 SLEDAI 评分相关（p=0.009 和 0.03），而 miR-124 与血红蛋白水平相关（p=0.03）。
miR-199a 是 LN 的独立预测因子，可能作为该疾病的诊断生物标志物。miR-146a 可能在 LN 发病机制中发挥重要作用。
