Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Rheumatology and Immunology, The First People's Hospital of Yancheng Affiliated with Nantong University, Yancheng, China.
Front Immunol. 2019 Jan 11;9:3099. doi: 10.3389/fimmu.2018.03099. eCollection 2018.
Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD. MicroRNA (miRNA) profiles in PBMC from new-onset AOSD patients without any treatment and healthy controls (HCs) were analyzed by miRNA deep sequencing. Plasma samples from 100 AOSD patients and 60 HCs were used to validated the expression levels of miRNA by qRT-PCR. The correlations between expression levels of miRNAs and clinical manifestations were analyzed using advanced statistical models. We found that plasma samples from AOSD patients showed a distinct miRNA expression profile. Five miRNAs (miR-142-5p, miR-101-3p, miR-29a-3p, miR-29c-3p, and miR-141-3p) were significantly upregulated in plasma of AOSD patients compared with HCs both in training and validation sets. We discovered a panel including 3 miRNAs (miR-142-5p, miR-101-3p, and miR-29a-3p) that can predict the probability of AOSD with an area under the receiver operating characteristic (ROC) curve of 0.8250 in training and validation sets. Moreover, the expression levels of 5 miRNAs were significantly higher in active AOSD patients compared with those in inactive patients. In addition, elevated level of miR-101-3p was found in AOSD patients with fever, sore throat and arthralgia symptoms; the miR-101-3p was also positively correlated with the levels of IL-6 and TNF-α in serum. Furthermore, five miRNAs (miR-142-5p, miR-101-3p, miR-29c-3p, miR-29a-3p, and miR-141-3p) expressed in plasma were significantly higher in AOSD patients than in sepsis patients ( < 0.05). The AUC value of 4-miRNA panel (miR-142-5p, miR-101-3p, miR-29c-3p, and miR-141-3p) for AOSD diagnosis from sepsis was 0.8448, revealing the potentially diagnostic value to distinguish AOSD patients from sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as a potential non-invasive biomarker for diagnosis of AOSD and monitoring disease activity.
成人斯蒂尔病（AOSD）是一种以细胞因子风暴为特征的系统性炎症性疾病。然而，尚未有临床验证的 AOSD 诊断测试。我们的研究旨在确定具有高特异性和灵敏度的非侵入性生物标志物，用于 AOSD 的诊断。通过 miRNA 深度测序分析新发病例 AOSD 患者和健康对照者（HC）外周血单个核细胞（PBMC）中的 microRNA（miRNA）谱。使用 qRT-PCR 验证了来自 100 名 AOSD 患者和 60 名 HCs 的血浆样本中的 miRNA 表达水平。使用先进的统计模型分析 miRNA 表达水平与临床表现之间的相关性。我们发现 AOSD 患者的血浆样本显示出明显的 miRNA 表达谱。在训练和验证组中，与 HCs 相比，AOSD 患者的血浆中 miR-142-5p、miR-101-3p、miR-29a-3p、miR-29c-3p 和 miR-141-3p 等 5 种 miRNA 明显上调。我们发现了一个包含 3 种 miRNA（miR-142-5p、miR-101-3p 和 miR-29a-3p）的 panel，在训练和验证组中，预测 AOSD 概率的受试者工作特征（ROC）曲线下面积（AUC）为 0.8250。此外，与无活性 AOSD 患者相比，活动期 AOSD 患者的 5 种 miRNA 表达水平明显升高。此外，在有发热、咽痛和关节痛症状的 AOSD 患者中发现 miR-101-3p 水平升高；miR-101-3p 与血清中 IL-6 和 TNF-α的水平呈正相关。此外，与败血症患者相比，miR-142-5p、miR-101-3p、miR-29c-3p、miR-29a-3p 和 miR-141-3p 等 5 种在血浆中表达的 miRNA 在 AOSD 患者中明显升高（<0.05）。用于区分 AOSD 患者和败血症患者的 4- miRNA 组（miR-142-5p、miR-101-3p、miR-29c-3p 和 miR-141-3p）的 AUC 值为 0.8448，表明其具有潜在的诊断价值。我们的研究结果确定了一种特定的血浆 miRNA 特征，它可能作为 AOSD 诊断和监测疾病活动的潜在非侵入性生物标志物。
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