Serum microRNA Profiles Serve as Novel Biomarkers for Autoimmune Diseases.

Serum microRNA Profiles Serve as Novel Biomarkers for Autoimmune Diseases.
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血清 microRNA 谱可作为自身免疫性疾病的新型生物标志物

DOI:
10.3389/fimmu.2018.02381
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发表时间:
2018
影响因子:
7.3
通讯作者:
Chen X
Chen X
中科院分区:
医学2区
文献类型:
--
作者:
Jin F;Hu H;Xu M;Zhan S;Wang Y;Zhang H;Chen X

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自身免疫性疾病涉及一种复杂的免疫失调。自身免疫性疾病包括许多成员[如类风湿性关节炎(RA)和系统性红斑狼疮(SLE)],其中大多数根据破坏性免疫反应所针对的器官和组织进行分类。许多研究都集中在寻找单一自身免疫性疾病的特异性生物标志物,但到目前为止,还没有通用的生物标志物来检测几乎所有的自身免疫性疾病。血清miRNAs已成为检测多种疾病的潜在生物标志物。本研究的目的是寻找一种诊断自身免疫性疾病的通用生物标志物。调节性T细胞(Tregs)在保护个体免受自身免疫中起着至关重要的作用,而Tregs在小鼠体内的缺失被认为是自身免疫性疾病的典型动物模型。用CD25mAb(C57小鼠)和白喉毒素(DT)(Foxp3DTR小鼠)两种Treg耗竭模型,在Treg耗竭小鼠的血清中检测到381个miRNAs。在Treg耗竭小鼠和自身免疫性疾病患者中发现了一种独特的循环miRNA图谱。QRT-PCR验证和ROC曲线分析确定,在Treg缺失的小鼠模型中,6个miRNAs(miR-551b、miR-448、miR-9、miR-124、miR-148和miR-34c)和3个miRNAs[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。这些循环中的miRNAs可能是自身免疫性疾病诊断和预后的潜在通用生物标志物。
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 Foxp3DTR 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.
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