State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, NJU Advanced Institute for Life Sciences, Nanjing University, Nanjing, China.
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Front Immunol. 2018 Oct 16;9:2381. doi: 10.3389/fimmu.2018.02381. eCollection 2018.
Autoimmune diseases involve a complex dysregulation of immunity. Autoimmune diseases include many members [e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)], and most of them are classified according to what organs and tissues are targeted by the damaging immune response. Many studies have focused on finding specific biomarkers for single autoimmune diseases, but so far, there are no universal biomarkers for detecting almost all autoimmune diseases. Serum miRNAs have served as potential biomarkers for detecting various diseases. The purpose of this study was to find a universal biomarker for diagnosing autoimmune diseases. Regulatory T cells (Tregs) play a crucial role in protecting an individual from autoimmunity, and depletion of Tregs in mice is considered a representative animal model of autoimmune disease. Two mouse models for Treg depletion, in which Treg was depleted by CD25mAb (in C57 mice) or by diphtheria toxin (DT) (in Foxp3 mice), were investigated, and 381 miRNAs were identified in the serum of mice with Treg depletion. A distinctive circulating miRNA profile was identified in Treg-depleted mice and in patients with autoimmune disease. QRT-PCR confirmation and ROC curve analysis determined that six miRNAs (miR-551b, miR-448, miR-9, miR-124, miR-148, and miR-34c) in the Treg-depleted mouse models and three miRNAs [miR-551b (specificity 73.5%, sensitivity 88.4%), miR-448 (specificity 82.4%, sensitivity 91.3%), and miR-124 (specificity 76.5%, sensitivity 91.3%)] in patients with RA, SLE, Sjogren's syndrome (SS), and ulcerative colitis (UC) could serve as valuable specific biomarkers. These circulating miRNAs may represent potential universal biomarkers for autoimmune diseases diagnosis and prognosis.
自身免疫性疾病涉及免疫的复杂失调。自身免疫性疾病包括许多成员[例如类风湿关节炎（RA）和系统性红斑狼疮（SLE）]，大多数根据受损免疫反应针对的器官和组织进行分类。许多研究都集中在寻找针对单一自身免疫性疾病的特定生物标志物上，但到目前为止，还没有用于检测几乎所有自身免疫性疾病的通用生物标志物。血清 microRNA 已被用作检测各种疾病的潜在生物标志物。本研究的目的是找到用于诊断自身免疫性疾病的通用生物标志物。调节性 T 细胞（Treg）在保护个体免受自身免疫方面起着至关重要的作用，而在小鼠中耗尽 Treg 被认为是自身免疫性疾病的代表性动物模型。研究了两种用于耗尽 Treg 的小鼠模型，其中一种是用 CD25mAb（在 C57 小鼠中）或白喉毒素（DT）（在 Foxp3 小鼠中）耗尽 Treg，在 Treg 耗尽的小鼠血清中鉴定出 381 个 microRNA。在 Treg 耗尽的小鼠和自身免疫性疾病患者中鉴定出独特的循环 microRNA 谱。通过 QRT-PCR 确认和 ROC 曲线分析确定，在 Treg 耗尽的小鼠模型中六种 microRNA（miR-551b、miR-448、miR-9、miR-124、miR-148 和 miR-34c）和三种 microRNA[miR-551b（特异性 73.5%，敏感性 88.4%）、miR-448（特异性 82.4%，敏感性 91.3%）和 miR-124（特异性 76.5%，敏感性 91.3%）]可作为有价值的特异性生物标志物。这些循环 microRNA 可能代表用于自身免疫性疾病诊断和预后的潜在通用生物标志物。
