Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Mol Immunol. 2018 Sep;101:531-538. doi: 10.1016/j.molimm.2018.07.029. Epub 2018 Aug 29.
This study aimed to determine the expression of circRNAs in plasma from lupus nephritis (LN) patients to identify novel biomarkers for LN screening. We initially performed microarray screening of circRNA changes in plasma from 5 L N patients, 5 systemic lupus erythematosus (SLE) patients without LN, and 5 healthy controls. We then confirmed the selected circRNA changes in plasma from 59 SLE patients (30 with LN and 29 without LN), 26 rheumatoid arthritis (RA) patients, and 27 age- and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction. Spearman's correlation test was performed to assess the correlation of circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. We confirmed that plasma circRNA_002453 was significantly elevated in LN patients when compared with SLE patients without LN, RA patients, and healthy controls. Plasma circRNA_002453 was also found to be upregulated in SLE patients when compared with RA patients and healthy controls. Among these LN patients, we detected no significant correlation between plasma circRNA_002453 and disease activity, including complement 3 (C3), complement 4 (C4), and SLE disease activity index 2000 (SLEDAI-2 K) score. However, its expression level was significantly and positively correlated with 24-hour proteinuria (r = 0.571, p = 0.001) and renal SLEDAI score (r = 0.640, p < 0.001). ROC analysis showed that plasma circRNA_002453 had an area under the curve of 0.906 (95% CI 0.838-0.974, p < 0.001) to discriminate LN patients from controls (SLE patients without LN, RA patients, and healthy controls) with sensitivity of 0.900 and specificity of 0.841. The highest Youden index was 0.741 and the corresponding optimal cut-off value was 0.001. This study suggests that upregulated plasma circRNA_002453 level in LN patients is associated with the severity of renal involvement and may also serve as a potential biomarker for LN patient diagnosis.
本研究旨在确定狼疮肾炎 (LN) 患者血浆中环状 RNA (circRNA) 的表达，以鉴定 LN 筛查的新型生物标志物。我们首先对 5 例 LN 患者、5 例无 LN 的系统性红斑狼疮 (SLE) 患者和 5 名健康对照者的血浆 circRNA 变化进行了微阵列筛选。然后，我们使用实时定量逆转录-聚合酶链反应（qRT-PCR）对来自 59 例 SLE 患者（30 例 LN 患者和 29 例无 LN 患者）、26 例类风湿关节炎 (RA) 患者和 27 名年龄和性别匹配的对照者的血浆中选定的 circRNA 变化进行了验证。采用 Spearman 相关检验评估 circRNA 与临床变量的相关性。绘制受试者工作特征 (ROC) 曲线以评估诊断价值。我们证实，与无 LN 的 SLE 患者、RA 患者和健康对照组相比，LN 患者血浆 circRNA_002453 显著升高。与 RA 患者和健康对照组相比，SLE 患者的血浆 circRNA_002453 也上调。在这些 LN 患者中，我们未检测到血浆 circRNA_002453 与疾病活动度（包括补体 3 [C3]、补体 4 [C4]和系统性红斑狼疮疾病活动指数 2000 [SLEDAI-2K] 评分）之间存在显著相关性。然而，其表达水平与 24 小时蛋白尿（r=0.571，p=0.001）和肾脏 SLEDAI 评分（r=0.640，p<0.001）显著正相关。ROC 分析显示，血浆 circRNA_002453 对 LN 患者与对照组（无 LN 的 SLE 患者、RA 患者和健康对照组）的区分具有 0.906 的曲线下面积（95%CI 0.838-0.974，p<0.001），其灵敏度为 0.900，特异性为 0.841。最大 Youden 指数为 0.741，最佳截断值为 0.001。本研究表明，LN 患者血浆中环状 RNA_002453 水平的上调与肾脏受累的严重程度相关，也可能作为 LN 患者诊断的潜在生物标志物。
