原发性进行性多发性硬化症患者脑脊液中的 miRNA 特征。
miRNA Signature in CSF From Patients With Primary Progressive Multiple Sclerosis.
机构信息
From the Neuroinflammation and Neurodegeneration Group (M.M.-S.M., I.G., A.Q.-V., M.G.R., R.R.C., G.Á., A.M., E.Q., L.R.-T.), Girona Biomedical Research Institute (IDIBGI), Salt, Spain; CERCA Programme/Generalitat de Catalunya; Neurology Department (R.R.C., G.Á., L.R.-T.), Girona Neuroimmunology and Multiple Sclerosis Unit, Dr. Josep Trueta University Hospital and Santa Caterina Hospital; Red Española de Esclerosis Múltiple (REEM) (R.R.C., E.Q., L.R.-T.) Medical Sciences Department (R.R.C., E.Q., L.R.-T.), University of Girona (UdG), Spain; Girona Biomedical Research Institute (IDIBGI) (M.B.), Spain; Immunology Department (L.M.V.), Hospital Ramón y Cajal, Madrid, Spain; IRYCIS; and Unitat de Neuroimmunologia, Hospital Universitari i Politècnic La Fe.València (J.C.-V., B.C.).
出版信息
Neurol Neuroimmunol Neuroinflamm. 2022 Dec 9;10(1). doi: 10.1212/NXI.0000000000200069. Print 2023 Jan.
BACKGROUND AND OBJECTIVES
Primary progressive multiple sclerosis (PPMS) displays a highly variable disease progression with a characteristic accumulation of disability, what makes difficult its diagnosis and efficient treatment. The identification of microRNAs (miRNAs)-based signature for the early detection in biological fluids could reveal promising biomarkers to provide new insights into defining MS clinical subtypes and potential therapeutic strategies. The objective of this cross-sectional study was to describe PPMS miRNA profiles in CSF and serum samples compared with other neurologic disease individuals (OND) and relapsing-remitting MS (RRMS).
METHODS
First, a screening stage analyzing multiple miRNAs in few samples using OpenArray plates was performed. Second, individual quantitative polymerase chain reactions (qPCRs) were used to validate specific miRNAs in a greater number of samples.
RESULTS
A specific profile of dysregulated circulating miRNAs (let-7b-5p and miR-143-3p) was found downregulated in PPMS CSF samples compared with OND. In addition, in serum samples, miR-20a-5p and miR-320b were dysregulated in PPMS against RRMS and OND, miR-26a-5p and miR-485-3p were downregulated in PPMS vs RRMS, and miR-142-5p was upregulated in RRMS compared with OND.
DISCUSSION
We described a 2-miRNA signature in CSF of PPMS individuals and several dysregulated miRNAs in serum from patients with MS, which could be considered valuable candidates to be further studied to unravel their actual role in MS.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that specific miRNA profiles accurately distinguish PPMS from RRMS and other neurologic disorders.
背景与目的
原发性进展型多发性硬化症（PPMS）表现出高度可变的疾病进展，其特征是残疾逐渐积累，这使得其诊断和有效治疗变得困难。在生物体液中识别基于 microRNAs（miRNAs）的特征性标志物可能会揭示有前途的生物标志物，为确定 MS 临床亚型和潜在治疗策略提供新的见解。本横断面研究的目的是描述与其他神经系统疾病个体（OND）和复发缓解型多发性硬化症（RRMS）相比，CSF 和血清样本中 PPMS 的 miRNA 图谱。
方法
首先，使用 OpenArray 板在少数样本中进行了多种 miRNA 的筛选阶段分析。其次，使用个体定量聚合酶链反应（qPCR）在更多样本中验证特定 miRNA。
结果
与 OND 相比，PPMS CSF 样本中发现循环 miRNAs（let-7b-5p 和 miR-143-3p）下调的特定失调特征。此外，在血清样本中，miR-20a-5p 和 miR-320b 在 PPMS 中与 RRMS 和 OND 失调，miR-26a-5p 和 miR-485-3p 在 PPMS 中下调，而 miR-142-5p 在 RRMS 中上调。
讨论
我们描述了 PPMS 个体 CSF 中的 2-miRNA 特征和 MS 患者血清中几种失调的 miRNAs，这可能被认为是有价值的候选物，以进一步研究揭示它们在 MS 中的实际作用。
证据分类
本研究提供了 II 级证据，表明特定的 miRNA 图谱可准确区分 PPMS 与 RRMS 和其他神经系统疾病。
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