Multiple sclerosis has a distinct lipid signature in plasma and cerebrospinal fluid

ABSTRACT The diagnosis of multiple sclerosis (MS) has changed over the last decade, but remains a composite of clinical assessment and magnetic resonance imaging to prove dissemination of lesions in time and space. The intrathecal synthesis of immunoglobulin may be a nonspecific marker and there are no plasma biomarkers that are useful in the diagnosis of MS, presenting additional challenges to their early detection. Methods We performed a preliminary untargeted qualitative lipidomics mass spectrometry analysis, comparing cerebrospinal fluid (CSF) and plasma samples from patients with MS, other inflammatory neurological diseases and idiopathic intracranial hypertension. Results Lipid identification revealed that fatty acids and sphingolipids were the most abundant classes of lipids in the CSF and that glycerolipids and fatty acids were the main class of lipids in the plasma of patients with MS. The area under the curve was 0.995 (0.912–1) and 0.78 (0.583–0.917), respectively. The permutation test indicated that this ion combination was useful for distinguishing MS from other inflammatory diseases (p < 0.001 and 0.055, respectively). Conclusion This study concluded that the CSF and plasma from patients with MS bear a unique lipid signature that can be useful as a diagnostic biomarker.

摘要 近十年来，多发性硬化（multiple sclerosis, MS）的诊断方式已发生变革，但其核心仍为结合临床评估与磁共振成像（magnetic resonance imaging）以证实病灶在时间与空间上的播散。免疫球蛋白鞘内合成或仅为非特异性标志物，目前尚无可用的多发性硬化诊断血浆生物标志物，这为其早期检测带来了额外挑战。
方法 本研究开展了一项初步的非靶向定性脂质组学质谱分析，对比多发性硬化患者、其他炎性神经系统疾病患者及特发性颅内高压患者的脑脊液（cerebrospinal fluid, CSF）与血浆样本。
结果 脂质鉴定结果显示，脑脊液中丰度最高的脂质类别为脂肪酸与鞘脂，而多发性硬化患者血浆中的主要脂质类别则为甘油脂与脂肪酸。针对两类样本的检测曲线下面积分别为0.995（95%置信区间：0.912~1）与0.78（95%置信区间：0.583~0.917）。置换检验结果表明，该离子组合可有效区分多发性硬化与其他炎性神经系统疾病，对应P值分别为<0.001与0.055。
结论 本研究证实，多发性硬化患者的脑脊液与血浆具有独特的脂质特征，可作为多发性硬化诊断的潜在生物标志物。