Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, United States.
Nebraska Center for Integrated Biomolecular Communication, University of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, United States.
ACS Chem Neurosci. 2024 Mar 20;15(6):1110-1124. doi: 10.1021/acschemneuro.3c00678. Epub 2024 Feb 29.
Multiple sclerosis (MS) is a chronic and progressive neurological disorder without a cure, but early intervention can slow disease progression and improve the quality of life for MS patients. Obtaining an accurate diagnosis for MS is an arduous and error-prone task that requires a combination of a detailed medical history, a comprehensive neurological exam, clinical tests such as magnetic resonance imaging, and the exclusion of other possible diseases. A simple and definitive biofluid test for MS does not exist, but is highly desirable. To address this need, we employed NMR-based metabolomics to identify potentially unique metabolite biomarkers of MS from a cohort of age and sex-matched samples of cerebrospinal fluid (CSF), serum, and urine from 206 progressive MS (PMS) patients, 46 relapsing-remitting MS (RRMS) patients, and 99 healthy volunteers without a MS diagnosis. We identified 32 metabolites in CSF that varied between the control and PMS patients. Utilizing patient-matched serum samples, we were able to further identify 31 serum metabolites that may serve as biomarkers for PMS patients. Lastly, we identified 14 urine metabolites associated with PMS. All potential biomarkers are associated with metabolic processes linked to the pathology of MS, such as demyelination and neuronal damage. Four metabolites with identical profiles across all three biofluids were discovered, which demonstrate their potential value as cross-biofluid markers of PMS. We further present a case for using metabolic profiles from PMS patients to delineate biomarkers of RRMS. Specifically, three metabolites exhibited a variation from healthy volunteers without MS through RRMS and PMS patients. The consistency of metabolite changes across multiple biofluids, combined with the reliability of a receiver operating characteristic classification, may provide a rapid diagnostic test for MS.
多发性硬化症（MS）是一种无法治愈的慢性进行性神经系统疾病，但早期干预可以减缓疾病进展，提高 MS 患者的生活质量。为 MS 患者做出准确的诊断是一项艰巨且容易出错的任务，需要结合详细的病史、全面的神经系统检查、磁共振成像等临床检查以及排除其他可能的疾病。目前尚不存在简单而明确的 MS 生物体液测试方法，但这是非常需要的。为了解决这一需求，我们采用基于 NMR 的代谢组学方法，从 206 名进展型 MS（PMS）患者、46 名复发缓解型 MS（RRMS）患者和 99 名无 MS 诊断的健康志愿者的年龄和性别匹配的脑脊液（CSF）、血清和尿液样本中鉴定出潜在的独特代谢物生物标志物。我们在 CSF 中鉴定出 32 种代谢物，这些代谢物在对照组和 PMS 患者之间存在差异。利用患者匹配的血清样本，我们进一步鉴定出 31 种可能作为 PMS 患者生物标志物的血清代谢物。最后，我们鉴定出 14 种与 PMS 相关的尿液代谢物。所有潜在的生物标志物都与代谢过程有关，这些代谢过程与 MS 的病理学有关，例如脱髓鞘和神经元损伤。我们发现了 4 种在所有三种生物体液中具有相同特征的代谢物，这表明它们作为 PMS 跨生物体液标志物的潜在价值。我们进一步提出了一个使用 PMS 患者代谢谱来描绘 RRMS 生物标志物的案例。具体来说，三种代谢物在健康志愿者、RRMS 患者和 PMS 患者中表现出不同的变化。跨多种生物体液的代谢物变化的一致性，加上接收器操作特性分类的可靠性，可能为 MS 提供一种快速诊断测试。
