Stoop Marcel P, Dekker Lennard J, Titulaer Mark K, Burgers Peter C, Sillevis Smitt Peter A E, Luider Theo M, Hintzen Rogier Q
Laboratories of Neuro-Oncology/Clinical and Cancer Proteomics, Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Proteomics. 2008 Apr;8(8):1576-85. doi: 10.1002/pmic.200700446.
A total of 164 cerebrospinal fluid (CSF) samples taken from neurological patients were classed into four groups according to the clinical diagnosis: multiple sclerosis (MScl, n = 44), clinically isolated syndrome of demyelination (CIS, n = 40), other inflammatory neurological disease (OIND, n = 26) and other neurological disease (OND, n = 54). After tryptic digestion, the samples were measured by MALDI-TOF MS. Spectra were analyzed using the R-project software package, in which a peak detection algorithm was developed. Subsequently, the peak lists were compared based on ranked data (non-parametric). Significant differences were observed in the comparisons of MScl vs. OND and CIS vs. OND. The comparisons of MScl vs. OIND, and CIS vs. OIND showed fewer significant differences. No significant differences were found in comparisons MScl vs. CIS and OIND vs. OND. MScl and CIS had strikingly similar profiles, probably a reflection of common pathological mechanisms. Three differentially expressed proteins in the comparison of MScl vs. OND were identified: chromogranin A, a potential marker for neurodegeneration; and two important factors in complement-mediated inflammatory reaction, clusterin and complement C3. CSF chromogranin A levels were confirmed to be significantly elevated in the MScl group using an ELISA.
从神经科患者采集的总共164份脑脊液（CSF）样本，根据临床诊断分为四组：多发性硬化症（MScl，n = 44）、临床孤立性脱髓鞘综合征（CIS，n = 40）、其他炎性神经疾病（OIND，n = 26）和其他神经疾病（OND，n = 54）。经胰蛋白酶消化后，采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）对样本进行检测。使用R-project软件包分析光谱，其中开发了一种峰检测算法。随后，基于排序数据（非参数）比较峰列表。在MScl与OND以及CIS与OND的比较中观察到显著差异。MScl与OIND以及CIS与OIND的比较显示出较少的显著差异。在MScl与CIS以及OIND与OND的比较中未发现显著差异。MScl和CIS具有惊人的相似谱图，这可能反映了共同的病理机制。在MScl与OND的比较中鉴定出三种差异表达蛋白：嗜铬粒蛋白A，一种神经退行性变的潜在标志物；以及补体介导的炎症反应中的两个重要因子，簇集蛋白和补体C3。使用酶联免疫吸附测定（ELISA）证实MScl组的脑脊液嗜铬粒蛋白A水平显著升高。
