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脑脊液硫酸脑苷脂同种型模式可区分进展型多发性硬化与复发缓解型多发性硬化。

Sulfatide isoform pattern in cerebrospinal fluid discriminates progressive MS from relapsing-remitting MS.

机构信息

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

J Neurochem. 2018 Aug;146(3):322-332. doi: 10.1111/jnc.14452. Epub 2018 Jul 3.

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Several biomarkers including proteins and lipids have been reported in MS cerebrospinal fluid (CSF), reflecting different aspects of the pathophysiology particularly of relapsing-remitting MS (RRMS). Sulfatide, abundant in the myelin sheath and a proposed target for autoimmune attack in MS, has been reported altered in MS CSF. Here, we investigated the potential of CSF sulfatide and its isoforms as biomarkers in MS. A highly sensitive and quantitative mass spectrometry method was employed to determine levels of sulfatide isoforms in CSF from RRMS and progressive MS (PMS) patients, and healthy donors (HD). We demonstrate that levels of total CSF sulfatide and C24:1, C26:1, and C26:1-OH isoforms were significantly increased in PMS compared with RRMS patients and HD, while C23:0-OH was significantly decreased in CSF from PMS patients compared to the other two groups. Multivariate discriminant analysis showed that CSF sulfatide isoform pattern in PMS patients was distinct and non-overlapping with that of RRMS patients and HD. Sulfatide levels did not correlate with tested biomarkers or clinical parameters. The results suggest that CSF sulfatide isoform levels may be used to discriminate the phenotype of MS and might play a role in the progression of the disease.

摘要

多发性硬化症(MS)是一种中枢神经系统(CNS)的炎症性脱髓鞘疾病。已经在多发性硬化症脑脊髓液(CSF)中报道了几种生物标志物,包括蛋白质和脂质,这些标志物反映了疾病的病理生理学的不同方面,特别是在复发缓解型多发性硬化症(RRMS)中。神经髓鞘中大量存在的神经节苷脂硫酸盐,被认为是多发性硬化症自身免疫攻击的靶标,已经有报道称其在多发性硬化症 CSF 中发生了改变。在这里,我们研究了 CSF 神经节苷脂硫酸盐及其异构体作为多发性硬化症生物标志物的潜力。我们采用高灵敏度和定量质谱法来测定 RRMS 和进行性多发性硬化症(PMS)患者以及健康供体(HD)的 CSF 中神经节苷脂硫酸盐异构体的水平。我们证明,与 RRMS 患者和 HD 相比,PMS 患者的总 CSF 神经节苷脂硫酸盐和 C24:1、C26:1 和 C26:1-OH 异构体的水平显着增加,而 PMS 患者 CSF 中的 C23:0-OH 显着减少与其他两组相比。多元判别分析表明,PMS 患者 CSF 神经节苷脂硫酸盐异构体模式与 RRMS 患者和 HD 明显不同且不重叠。神经节苷脂水平与测试的生物标志物或临床参数无关。结果表明,CSF 神经节苷脂硫酸盐异构体水平可能用于区分 MS 的表型,并且可能在疾病的进展中起作用。

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