Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis
Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis
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DOI：
10.1177/1352458513477923
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发表时间：
2013-10-01
影响因子：
5.8
通讯作者：
Sadiq, Saud A.
中科院分区：
文献类型：
--
作者：
Harris, Violaine K.;Donelan, Nicola;Sadiq, Saud A.
背景：多发性硬化症 (MS) 迫切需要能够可靠地测量与炎症、神经变性和脱髓鞘/髓鞘再生相关的持续疾病活动的生物标志物。胎球蛋白-A 最近被确定为 MS 脑脊液 (CSF) 中的潜在生物标志物。胎球蛋白-A 具有多种功能，包括在免疫途径中发挥作用。 目的：本研究的目的是调查胎球蛋白-A 是否是疾病活动性的直接指标。方法：我们测量了 MS 患者脑脊液和血浆中的胎球蛋白-A，并将这些结果与临床疾病活动性和那他珠单抗反应相关联。在 MS 脑组织和实验性自身免疫性脑脊髓炎 (EAE) 小鼠中对胎球蛋白-A 的表达进行了表征。我们还使用胎球蛋白-A 缺陷小鼠检查了胎球蛋白-A 在 EAE 中的致病作用。结果：脑脊液胎球蛋白-A 升高与 MS 疾病活动相关。在那他珠单抗治疗的患者中，治疗一年后脑脊液胎球蛋白 A 水平降低，与治疗反应相关。胎球蛋白-A 在脱髓鞘病变和多发性硬化症脑组织内的灰质中显着升高。同样，EAE 脱髓鞘病变周围的退化神经元中胎球蛋白 A 升高。胎球蛋白-A 缺陷小鼠表现出 EAE 症状的延迟发作和严重程度降低。结论：我们的结果表明，脑脊液胎球蛋白-A 是 MS 中疾病活动性和那他珠单抗反应的生物标志物。胎球蛋白-A 的神经元表达表明胎球蛋白-A 可能在疾病过程中发挥病理作用。
Background: There is an urgent need for biomarkers in multiple sclerosis (MS) that can reliably measure ongoing disease activity relative to inflammation, neurodegeneration, and demyelination/remyelination. Fetuin-A was recently identified as a potential biomarker in MS cerebrospinal fluid (CSF). Fetuin-A has diverse functions, including a role in immune pathways.Objective: The objective of this research is to investigate whether fetuin-A is a direct indicator of disease activity.Methods: We measured fetuin-A in CSF and plasma of patients with MS and correlated these findings to clinical disease activity and natalizumab response. Fetuin-A expression was characterized in MS brain tissue and in experimental autoimmune encephalomyelitis (EAE) mice. We also examined the pathogenic role of fetuin-A in EAE using fetuin-A-deficient mice.Results: Elevated CSF fetuin-A correlated with disease activity in MS. In natalizumab-treated patients, CSF fetuin-A levels were reduced one year post-treatment, correlating with therapeutic response. Fetuin-A was markedly elevated in demyelinated lesions and in gray matter within MS brain tissue. Similarly, fetuin-A was elevated in degenerating neurons around demyelinated lesions in EAE. Fetuin-A-deficient mice demonstrated delayed onset and reduced severity of EAE symptoms.Conclusions: Our results show that CSF fetuin-A is a biomarker of disease activity and natalizumab response in MS. Neuronal expression of fetuin-A suggests that fetuin-A may play a pathological role in the disease process.