Lehmensiek V, Süssmuth S D, Tauscher G, Brettschneider J, Felk S, Gillardon F, Tumani H
Department of Neurology, University of Ulm, 89081, Ulm, Germany.
Mult Scler. 2007 Aug;13(7):840-9. doi: 10.1177/1352458507076406.
Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment. Using the two-dimensional difference gel electrophoresis (2-D-DIGE) technology for comparative analysis, we compared CSF samples from patients with MS of the relapse-remitting type (RRMS, n = 12) and from patients with clinically isolated syndrome (CIS, n = 12) suggestive of a first demyelinating attack with neurologically normal controls. Protein spots that showed more than two-fold difference between patients and controls were selected for further analysis with MALDI-TOF mass spectrometry. Immunoblot analysis was performed to confirm the validity of individual candidate proteins. In RRMS, we identified 1 up-regulated and 10 down-regulated proteins. In CIS, 2 up-regulated and 11 down-regulated proteins were identified. One of these proteins (Apolipoprotein A1) was confirmed by immunoblot. Though the pathophysiological role of these proteins still remains to be elucidated in detail and further validation is needed, these findings may have a relevant impact on the identification of disease-specific markers.
脑脊液(CSF)蛋白可能为多发性硬化症(MS)存在的病理机制提供重要信息。尽管早期MS的诊断标准已经存在,但仍需要生物标志物来预测疾病亚型和进展,以改善个体化治疗。我们使用二维差异凝胶电泳(2-D-DIGE)技术进行比较分析,将复发缓解型多发性硬化症(RRMS,n = 12)患者和提示首次脱髓鞘发作的临床孤立综合征(CIS,n = 12)患者的脑脊液样本与神经功能正常的对照进行比较。选择患者与对照之间差异超过两倍的蛋白点,用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF)进行进一步分析。进行免疫印迹分析以确认单个候选蛋白的有效性。在RRMS中,我们鉴定出1种上调蛋白和10种下调蛋白。在CIS中,鉴定出2种上调蛋白和11种下调蛋白。其中一种蛋白(载脂蛋白A1)通过免疫印迹得到证实。尽管这些蛋白的病理生理作用仍有待详细阐明且需要进一步验证,但这些发现可能对疾病特异性标志物的鉴定产生相关影响。