Sol Nik, Leurs Cyra E, Veld Sjors Gjg In 't, Strijbis Eva M, Vancura Adrienne, Schweiger Markus W, Teunissen Charlotte E, Mateen Farrah J, Tannous Bakhos A, Best Myron G, Würdinger Thomas, Killestein Joep
Department of Neurology, Neuroscience Amsterdam, VUmc MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands.
Brain Tumor Center Amsterdam, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands.
Mult Scler J Exp Transl Clin. 2020 Jul 30;6(3):2055217320946784. doi: 10.1177/2055217320946784. eCollection 2020 Jul-Sep.
In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. However, no blood biomarker has been confirmed as a useful tool in the diagnostic work-up.
Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development but also during platelet formation and platelet circulation. In this proof of concept study, we evaluate the diagnostic potential of spliced blood platelet RNA for the detection of MS.
We isolated and sequenced platelet RNA of blood samples obtained from 57 MS patients and 66 age- and gender-matched healthy controls (HCs). 60% was used to develop a particle swarm-optimized (PSO) support vector machine classification algorithm. The remaining 40% served as an independent validation series.
In total, 1249 RNAs with differential spliced junction expression levels were identified between platelets of MS patients as compared to HCs, including EPSTI1, IFI6, and RPS6KA3, in line with reported inflammatory signatures in the blood of MS patients. The RNAs were subsequently used as input for a MS classifier, capable of detecting MS with 80% accuracy in the independent validation series.
Spliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation.
在多发性硬化症（MS）中，临床评估、磁共振成像（MRI）和脑脊液在诊断过程中很重要。然而，尚未有血液生物标志物被确认为诊断检查中的有用工具。
血小板含有丰富的剪接mRNA库，其在巨核细胞发育过程中会发生变化，在血小板形成和血小板循环过程中也会发生变化。在这项概念验证研究中，我们评估了剪接血小板RNA在检测MS方面的诊断潜力。
我们分离并测序了从57例MS患者和66例年龄及性别匹配的健康对照（HCs）获得的血液样本中的血小板RNA。60%用于开发粒子群优化（PSO）支持向量机分类算法。其余40%用作独立验证系列。
与HCs相比，在MS患者的血小板之间总共鉴定出1249种具有差异剪接连接表达水平的RNA，包括EPSTI1、IFI6和RPS6KA3，这与MS患者血液中报道的炎症特征一致。这些RNA随后被用作MS分类器的输入，该分类器在独立验证系列中能够以80%的准确率检测MS。
剪接血小板RNA可能实现基于血液的MS诊断，值得进行大规模验证。
