Levels of clusterin, CD5L, ficolin-3, and gelsolin in ALS patients and controls

In amyotrophic lateral sclerosis, there is a need for biomarkers to distinguish patients from controls, to follow disease progression and to provide information about the pathogenesis of disease. In a previous mass spectrometry study that searched for potential proteins of interest, we identified clusterin, CD5L, ficolin-3, and gelsolin as molecules that differed in abundance between ALS patients and controls, with a greater difference in patients with cognitive impairment. Here, we have measured levels of these molecules in plasma from a separate cohort of ALS patients and controls. The plasma was depleted of abundant plasma proteins. We confirmed our previous findings that levels of clusterin are decreased and ficolin-3 are increased in ALS patients compared to controls. In this study, we found that levels of CD5L were increased in patients with ALS and levels correlated with survival. We found that levels of gelsolin were modestly increased in ALS compared to controls whereas in our previous study these were decreased, especially in patients with cognitive impairment who were not included in this study. We suggest that clusterin and ficolin-3 deserve further study as potential ALS biomarkers.

在肌萎缩侧索硬化症（amyotrophic lateral sclerosis, ALS）中，亟需找到可用于区分患者与健康对照、监测疾病进展，并揭示疾病发病机制的生物标志物。在既往一项筛选潜在目标蛋白的质谱分析研究中，我们鉴定出簇蛋白（clusterin）、CD5L、纤维胶凝蛋白-3（ficolin-3）与凝溶胶蛋白（gelsolin）在ALS患者与健康对照的血浆丰度存在差异，且在伴有认知障碍的患者中该差异更为显著。本研究中，我们对另一独立队列的ALS患者及健康对照的血浆样本中的上述分子水平进行了检测，该血浆样本已预先去除高丰度血浆蛋白。我们验证了既往研究结果：与健康对照相比，ALS患者体内的簇蛋白水平降低，而纤维胶凝蛋白-3水平升高。本研究还发现，ALS患者体内的CD5L水平升高，且该水平与患者生存期呈显著相关。我们观察到，与健康对照相比，本研究中ALS患者的凝溶胶蛋白水平呈轻度升高；但在既往研究中，该蛋白水平却呈降低趋势，且在伴认知障碍的患者中尤为明显——而本研究队列并未纳入此类患者。我们认为，簇蛋白与纤维胶凝蛋白-3有望作为ALS的潜在生物标志物，值得开展进一步研究。