Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Lupus. 2024 Sep;33(10):1089-1099. doi: 10.1177/09612033241266988. Epub 2024 Jul 22.
Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients.
LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RT‒qPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAI‒2K) score from 72 SLE patients was assessed by Spearman's test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the Mann‒Whitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis.
The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs.
LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.
越来越多的证据表明,长非编码 RNA(lncRNA)可能在系统性红斑狼疮(SLE)的发病机制中发挥重要作用,然而,lncRNA 对 SLE 的贡献在很大程度上仍不清楚。本研究旨在探讨 SLE 患者外周血单个核细胞(PBMC)中的 lncRNA 表达谱。
使用 lncRNA 测序技术检测 5 例 SLE-MIX 样本和 3 例健康对照(HC)-MIX 样本中 PBMC 的差异表达基因,并通过实时定量聚合酶链反应(RT-qPCR)进一步验证所选 lncRNA 的表达。通过 Spearman 检验评估 72 例 SLE 患者的 lncRNA 表达与实验室指标以及 SLE 疾病活动指数 2000(SLEDAI-2K)评分的相关性。通过 Mann-Whitney U 检验确定 lncRNA ENST00000597482 与 SLE 患者器官受累的相关性。此外,通过流式细胞术测量 SLE 患者外周血中的淋巴细胞亚群。另外,通过接受者操作特征(ROC)曲线分析评估 lncRNA 在预测 SLE 中的诊断价值。
lncRNA 表达谱显示,与健康对照组相比,SLE 患者 PBMC 中有 218 个差异表达的 lncRNA,包括 121 个上调基因和 97 个下调基因。在 10 个候选基因中,只有 lncRNA ENST00000597482 在 SLE PBMC 中的表达低于健康对照组,这与测序结果一致。lncRNA ENST00000597482 的表达与 SLEDAI-2K 评分以及抗核抗体和抗双链 DNA(抗 dsDNA)抗体的滴度呈负相关。值得注意的是,lncRNA ENST00000597482 表达水平较低的 SLE 患者易发生器官受累。此外,lncRNA ENST00000597482 在区分 SLE 患者和健康对照方面具有潜在的诊断价值。
SLE 患者 PBMC 中的 lncRNA ENST00000597482 表达低于健康对照组,与 SLEDAI-2K 评分和自身抗体滴度呈负相关。此外,lncRNA ENST00000597482 可作为疾病活动和 SLE 诊断的新型生物标志物。