Biomarkers of therapeutic response in multiple sclerosis: current status.
Biomarkers of therapeutic response in multiple sclerosis: current status.
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DOI：
10.1007/s40291-014-0117-0
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发表时间：
2014-12
影响因子：
4
通讯作者：
Sadiq SA
中科院分区：
文献类型：
--
作者：
Harris VK;Sadiq SA
多发性硬化（MS）是一种病因不明的自身免疫性疾病，其中慢性炎症驱动CNS中的白色和灰质中的轴突的多灶性脱髓鞘。该疾病的病理过程是异质性的，并且涉及复发-缓解型MS（RRMS）的早期、主要是炎性脱髓鞘疾病阶段，其在可变的时间段内演变成与轴突损失和瘢痕形成相关的进行性退行性阶段，导致身体和认知残疾。对于RRMS患者，有越来越多的疾病修饰剂（DMA），具有不同程度的疗效，如降低复发率，改善磁共振成像结果和保留神经功能所定义的。建立个性化的治疗计划仍然是MS治疗决策的最大挑战之一，因为疾病预后和个体治疗结果非常难以预测。目前的研究旨在发现和验证可靠测量疾病进展和有效治疗干预的生物标志物。具有明显临床实用性的个体生物标志物候选物在本综述中突出显示，包括针对DMA、胎球蛋白-A、骨桥蛋白、异前列腺素、趋化因子（C-X-C基序）配体13（CXCL 13）、神经丝轻和重以及几丁质酶3样蛋白的中和自身抗体。此外，更先进的筛选技术的应用开辟了新的生物标志物类别，这些生物标志物超越了单个可溶性蛋白的检测，包括基因表达和自身抗体阵列，microRNA和循环微泡/外泌体。在MS中开发临床上有用的生物标志物不仅将塑造个性化医学的实践，而且还将作为替代标志物，使临床试验中的创新治疗研究成本更低，持续时间更短，结果更确定。
Multiple sclerosis (MS) is an autoimmune disease of unknown cause, in which chronic inflammation drives multifocal demyelination of axons in both white and gray matter in the CNS. The pathological course of the disease is heterogeneous and involves an early, predominantly inflammatory demyelinating disease phase of relapsing–remitting MS (RRMS), which, over a variable period of time, evolves into a progressively degenerative stage associated with axonal loss and scar formation, causing physical and cognitive disability. For patients with RRMS, there is a growing arsenal of disease-modifying agents (DMAs), with varying degrees of efficacy, as defined by reduced relapse rates, improved magnetic resonance imaging outcomes, and preservation of neurological function. Establishment of personalized treatment plans remains one of the biggest challenges in therapeutic decision-making in MS because the disease prognosis and individual therapeutic outcomes are extremely difficult to predict. Current research is aimed at discovery and validation of biomarkers that reliably measure disease progression and effective therapeutic intervention. Individual biomarker candidates with evident clinical utility are highlighted in this review and include neutralizing autoantibodies against DMAs, fetuin-A, osteopontin, isoprostanes, chemokine (C-X-C motif) ligand 13 (CXCL13), neurofilament light and heavy, and chitinase 3-like protein. In addition, application of more advanced screening technologies has opened up new categories of biomarkers that move beyond detection of individual soluble proteins, including gene expression and autoantibody arrays, microRNAs, and circulating microvesicles/exosomes. Development of clinically useful biomarkers in MS will not only shape the practice of personalized medicine but will also serve as surrogate markers to enable investigation of innovative treatments within clinical trials that are less costly, are of shorter duration, and have more certainty of outcomes.
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基因与复发和缓解中的基因分型和表达谱的合伙性有关多发性硬化症发病机理。
影响因子：
--
作者：
Arthur, Ariel T.;Armati, Patricia J.;Bye, Chris;Heard, Robert N. S.;Stewart, Graeme J.;Pollard, John D.;Booth, David R.
通讯作者：
Booth, David R.
影响因子：
14.5
作者：
Comabella, M.;Luenemann, J. D.;Martin, R.
通讯作者：
Martin, R.
影响因子：
4.4
作者：
Defer, Gilles;Mariotte, Delphine;Le Mauff, Brigitte
通讯作者：
Le Mauff, Brigitte
影响因子：
3.3
作者：
Beyer, Natascha Helena;Lueking, Angelika;Heegaard, Niels H. H.
通讯作者：
Heegaard, Niels H. H.
影响因子：
158.5
作者：
Bloomgren, Gary;Richman, Sandra;Bozic, Carmen
通讯作者：
Bozic, Carmen