Department of Rheumatology, Renji Hospital, Shanghai Institute of Rheumatology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.
Rheumatology (Oxford). 2021 Apr 6;60(4):1734-1746. doi: 10.1093/rheumatology/keaa575.
The long non-coding RNA plays an important role in inflammation and autoimmune diseases. The aim of this study is to screen and identify abnormally expressed lncRNAs in peripheral blood neutrophils of SLE patients as novel biomarkers and to explore the relationship between lncRNAs levels and clinical features, disease activity and organ damage.
RNA-seq technology was used to screen differentially expressed lncRNAs in neutrophils from SLE patients and healthy donors. Based on the results of screening, candidate lncRNA levels in neutrophils of 88 SLE patients, 35 other connective disease controls, and 78 healthy controls were qualified by real-time quantitative polymerase chain reaction.
LncRNA expression profiling revealed 360 up-regulated lncRNAs and 224 down-regulated lncRNAs in neutrophils of SLE patients when compared with healthy controls. qPCR assay validated that the expression of Lnc-FOSB-1:1 was significantly decreased in neutrophils of SLE patients when compared with other CTD patients or healthy controls. It correlated negatively with SLE Disease Activity Index 2000 (SLEDAI-2K) score (r = -0.541, P < 0.001) and IFN scores (r = -0.337, P = 0.001). More importantly, decreased Lnc-FOSB-1:1 expression was associated with lupus nephritis. Lower baseline Lnc-FOSB-1:1 level was associated with higher risk of future renal involvement (within an average of 2.6 years) in patients without renal disease at baseline (P = 0.019).
LncRNA expression profile in neutrophils of SLE patients revealed differentially expressed lncRNAs. Validation study on Lnc-FOSB-1:1 suggest that it is a potential biomarker for prediction of near future renal involvement.
长链非编码 RNA 在炎症和自身免疫性疾病中发挥重要作用。本研究旨在筛选和鉴定系统性红斑狼疮(SLE)患者外周血中性粒细胞中异常表达的 lncRNA,作为新的生物标志物,并探讨 lncRNA 水平与临床特征、疾病活动度和器官损伤的关系。
采用 RNA-seq 技术筛选 SLE 患者和健康供者中性粒细胞中差异表达的 lncRNA。基于筛选结果,采用实时定量聚合酶链反应(qPCR)技术对 88 例 SLE 患者、35 例其他结缔组织病(CTD)对照和 78 例健康对照的中性粒细胞中候选 lncRNA 水平进行了验证。
lncRNA 表达谱分析显示,与健康对照相比,SLE 患者中性粒细胞中 360 个 lncRNA 上调,224 个 lncRNA 下调。qPCR 检测验证了 Lnc-FOSB-1:1 在 SLE 患者中性粒细胞中的表达明显低于其他 CTD 患者或健康对照。它与 SLE 疾病活动指数 2000(SLEDAI-2K)评分(r=-0.541,P<0.001)和 IFN 评分(r=-0.337,P=0.001)呈负相关。更重要的是,下调的 Lnc-FOSB-1:1 表达与狼疮肾炎有关。基线时 Lnc-FOSB-1:1 表达水平较低与基线时无肾脏疾病的患者未来发生肾脏受累的风险增加(平均 2.6 年内)相关(P=0.019)。
SLE 患者中性粒细胞的 lncRNA 表达谱显示差异表达的 lncRNA。对 Lnc-FOSB-1:1 的验证研究表明,它是预测近期肾脏受累的潜在生物标志物。