Voortman M M, Pekar T, Bachmayer D, Archelos J-J, Stojakovic T, Scharnagl H, Ropele S, Pichler A, Enzinger C, Fuchs S, Fazekas F, Seifert-Held T, Khalil M
Department of Neurology, Medical University of Graz, Austria.
University of Applied Sciences Wiener Neustadt, Austria.
Mult Scler J Exp Transl Clin. 2017 Aug 23;3(3):2055217317727294. doi: 10.1177/2055217317727294. eCollection 2017 Jul-Sep.
Netrin-1, a secreted laminin-related protein, is known to regulate not only axonal guidance and neuronal cell migration, but also blood-brain barrier integrity and inflammation. Two preliminary studies reported altered serum netrin-1 levels in multiple sclerosis; however, associations with longitudinal clinical and magnetic resonance imaging activity have not been investigated.
We aimed to assess serum netrin-1 in multiple sclerosis and controls with respect to disease activity and its temporal dynamics.
Serum netrin-1 was assessed by enzyme-linked immunosorbent assay in 79 patients with clinically isolated syndrome or multiple sclerosis, and 30 non-inflammatory neurological disease controls. In patients, serum samples were collected immediately prior to gadolinium-enhanced 3 T magnetic resonance imaging at two time points (initial contrast-enhancing gadolinium+ = 47, non-enhancing gadolinium- = 32; reference gadolinium- = 70; median time-lag 1.4, interquartile range 1.0-2.3 years).
Serum netrin-1 levels were similar in clinically isolated syndrome, multiple sclerosis and controls, and gadolinium+ and gadolinium- patients. Among gadolinium+ patients, serum netrin-1 was decreased in clinically active ( = 8) vs non-active patients ( = 39; = 0.041). Serum netrin-1 showed no temporal dynamics in multiple sclerosis and was unrelated to clinical data.
Serum netrin-1 levels show no multiple sclerosis specific changes and are not sensitive for detection of subclinical disease activity. Netrin-1 changes during relapses may deserve further examination.
Netrin-1是一种分泌型层粘连蛋白相关蛋白，已知其不仅可调节轴突导向和神经元细胞迁移，还可调节血脑屏障完整性和炎症。两项初步研究报告了多发性硬化症患者血清Netrin-1水平的改变；然而，尚未研究其与纵向临床和磁共振成像活动的相关性。
我们旨在评估多发性硬化症患者和对照组血清Netrin-1水平与疾病活动及其时间动态变化的关系。
采用酶联免疫吸附测定法评估79例临床孤立综合征或多发性硬化症患者及30例非炎性神经系统疾病对照者的血清Netrin-1水平。在患者中，于两个时间点在钆增强3T磁共振成像前立即采集血清样本（初始钆增强阳性=47例，钆增强阴性=32例；参考钆增强阴性=70例；中位时间间隔1.4年，四分位间距1.0 - 2.3年）。
临床孤立综合征、多发性硬化症患者及对照组，以及钆增强阳性和钆增强阴性患者的血清Netrin-1水平相似。在钆增强阳性患者中，临床活动期患者（=8例）的血清Netrin-1水平低于非活动期患者（=39例；=0.041）。血清Netrin-1在多发性硬化症中未显示出时间动态变化，且与临床数据无关。
血清Netrin-1水平未显示出多发性硬化症特异性变化，对亚临床疾病活动的检测不敏感。复发期间Netrin-1的变化可能值得进一步研究。
