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血液和脑脊液中多发性硬化症的新兴生物标志物:聚焦神经丝蛋白及治疗考量

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations.

作者信息

Biernacki Tamás, Kokas Zsófia, Sandi Dániel, Füvesi Judit, Fricska-Nagy Zsanett, Faragó Péter, Kincses Tamás Zsigmond, Klivényi Péter, Bencsik Krisztina, Vécsei László

机构信息

Albert Szent-Györgyi Clinical Centre, Department of Neurology, Faculty of General Medicine, University of Szeged, 6725 Szeged, Hungary.

Albert Szent-Györgyi Clinical Centre, Department of Radiology, Albert Szent-Györgyi Faculty of Medicine, University of Szeged, 6725 Szeged, Hungary.

出版信息

Int J Mol Sci. 2022 Mar 21;23(6):3383. doi: 10.3390/ijms23063383.

Abstract

INTRODUCTION

Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient's health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients.

AREAS COVERED

In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients.

DISCUSSION

the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

摘要

引言

多发性硬化症(MS)是影响年轻人的最常见的中枢神经系统(CNS)免疫介导的慢性神经退行性疾病。这是由于其导致的永久性残疾、认知障碍,以及MS对患者健康相关生活质量产生的巨大不利影响。及时识别并在早期开始适当治疗非常重要。目前使用的疾病修正疗法(DMT)旨在降低疾病活动度,从而阻止残疾发展,在当前临床实践中,这是通过临床和影像学参数而非血液和/或脑脊液(CSF)中的生物标志物来监测的。常规用于监测疾病活动度的临床和放射学措施均缺乏关于MS基本病理生理特征和机制的信息。此外,它们滞后于疾病进程本身。当临床复发明显或MRI扫描出现新病灶时,中枢神经系统可能已经发生了潜在的不可逆损伤。近年来,一些先前与其他神经和免疫疾病相关的生物标志物在MS中受到了越来越多的关注。此外,在MS患者的脑脊液和血液中还检测到了其他具有预后和诊断特性的新型潜在生物标志物。

涵盖领域

在本综述中,我们总结了对MS患者脑脊液和血液中已发现的已知且最有前景的新生物标志物候选物所进行的最新知识和研究。

讨论

MS目前的诊断标准依赖于三个支柱:MRI成像、临床事件以及脑脊液中寡克隆带的存在(在最新修订版中重新纳入诊断标准)。尽管最新的麦克唐纳标准使MS的诊断比之前的版本更快,但它仍然不是一个万无一失的诊断工具集,尤其是在临床孤立综合征的非常早期阶段。与金标准MRI和临床措施一起,辅助性血液和脑脊液生物标志物不仅可以提高诊断准确性和速度,而且很可能在不久的将来成为监测治疗效果并使MS的个性化治疗更加切实可行的手段。过去这些生物标志物的主要缺点是需要获取脑脊液来测量它们。然而,超灵敏免疫测定技术的最新进展使得即使它们仅以极小的浓度存在于外周血中也能够进行测量。这应该标志着MS生物标志物研究和利用新时代的开始。

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