Zhang Huidi, Huang Xixi, Ye Lulu, Guo Gangqiang, Li Xiao, Chen Chaosheng, Sun Li, Li Baoqing, Chen Nan, Xue Xiangyang
Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
School of the 2nd Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Front Immunol. 2018 Jun 29;9:1473. doi: 10.3389/fimmu.2018.01473. eCollection 2018.
Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls ( < 0.05) and could act as the diagnostic signature to distinguish SLE patients from healthy donors. Six miRNAs (miR-92a, miR-27a, miR-19b, miR-23a, miR-223, and miR-16) expressed in plasma were significantly lower in SLE patients than in RA patients ( < 0.05), revealing the potentially diagnostic signature to distinguish SLE patients from RA patients. Furthermore, the downregulated expression of miR-19b, miR-25, miR-93, and miR-15b was associated with SLE disease activity ( < 0.05) while miR-15b and miR-22 expressions were significantly lower in SLE patients with low estimate glomerular filtration rate (eGFR < 60 ml/min/1.73 m) ( < 0.05). The diagnostic potential of miR-15b for SLE disease activity and lupus nephritis (LN) with low eGFR was validated on an independent validation set with 69 SLE patients and a cross-validation set with 80 SLE patients. In summary, the signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and evaluation of disease activity and LN.
我们对与系统性红斑狼疮（SLE）相关的循环微小RNA（miRNA）的了解仍然非常有限。在本研究中，我们使用miRNA PCR阵列从42种B细胞相关miRNA中筛选SLE特异性miRNA。首先在50例SLE患者、16例类风湿关节炎（RA）患者和20例健康供体的血浆样本中使用qRT-PCR对所选miRNA进行确认。然后我们研究了所选miRNA的表达与SLE临床指标之间的关系。结果，与健康对照相比，SLE患者血浆中有14种miRNA（miR-103、miR-150、miR-20a、miR-223、miR-27a、miR-15b、miR-16、miR-181a、miR-19b、miR-22、miR-23a、miR-25、miR-92a和miR-93）显著降低（<0.05），并且可以作为区分SLE患者和健康供体的诊断标志物。血浆中表达的6种miRNA（miR-92a、miR-27a、miR-19b、miR-23a、miR-223和miR-16）在SLE患者中显著低于RA患者（<0.05），揭示了区分SLE患者和RA患者的潜在诊断标志物。此外，miR-19b、miR-25、miR-93和miR-15b的表达下调与SLE疾病活动相关（<0.05），而在估算肾小球滤过率低（eGFR<60 ml/min/1.73 m²）的SLE患者中，miR-15b和miR-22的表达显著降低（<0.05）。在一个包含69例SLE患者的独立验证集和一个包含80例SLE患者的交叉验证集中验证了miR-15b对SLE疾病活动和低eGFR狼疮性肾炎（LN）的诊断潜力。总之，循环miRNA标志物将为SLE的诊断、疾病活动评估和LN提供新的生物标志物。
