Li Dongpei, Usuki Seigo, Quarles Brandy, Rivner Michael H, Ariga Toshio, Yu Robert K
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, GA, USA.
Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Science, Frontier Research Center for Advanced Material and Life Science, Hokkaido University, Sapporo, Japan.
ASN Neuro. 2016 Sep 28;8(5). doi: 10.1177/1759091416669619. Print 2016 Oct.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS patients and 50 healthy controls, by means of enzyme-linked immunosorbent assay with affinity parametric complex criterion evaluation and thin-layer chromatography immunooverlay (immuno-TLC). Anti-SGPG antibodies were found in the sera of 13.3% ALS patients (15 out of 113). The highest titer reached 1:1600. The presence of anti-SGPG antibodies in the serum samples was also confirmed by immuno-TLC. Importantly, a multiple logistic regression analysis showed that the presence of anti-SGPG antibody was positively correlated with age (p < .01) and negatively correlated with ALS Functional Rating Scale score (p < .05). Moreover, the localization of SGPG-immunoreactivity on the motor neurons of rat spinal cord and a mouse motor neuronal cell line, NSC-34 was observed by an immunofluorescence method. These data suggest that SGPG could represent a specific pathogenic antigen in those ALS patients. The presence of anti-SGPG antibodies in the serum of ALS patients should represent a diagnostic biomarker of ALS, and it could reflect the severity of the disease.
肌萎缩侧索硬化症(ALS)是一种神经退行性疾病,其特征是上下运动神经元进行性退化。尽管ALS的病因尚不清楚,但家族性ALS的基因研究表明该病症存在多因素病因。同样,散发性ALS可能也有多种病因。自身免疫介导的运动神经元功能障碍是散发性ALS的一种病因假说。在本研究中,通过采用具有亲和力参数复合标准评估的酶联免疫吸附测定法和薄层色谱免疫印迹法(免疫TLC),对大量患者样本(包括113例ALS患者和50例健康对照)的血清中的抗糖脂抗体(包括GM1、GD1b、GD3和硫酸葡糖醛酸基副球蛋白(SGPG))进行了检测。在13.3%的ALS患者血清中发现了抗SGPG抗体(113例中有15例)。最高滴度达到1:1600。免疫TLC也证实了血清样本中存在抗SGPG抗体。重要的是,多元逻辑回归分析表明,抗SGPG抗体的存在与年龄呈正相关(p < .01),与ALS功能评定量表评分呈负相关(p < .05)。此外,通过免疫荧光法观察到SGPG免疫反应性在大鼠脊髓运动神经元和小鼠运动神经元细胞系NSC-34上的定位。这些数据表明,SGPG可能是那些ALS患者中的一种特异性致病抗原。ALS患者血清中抗SGPG抗体的存在应代表ALS的一种诊断生物标志物,并且它可以反映疾病的严重程度。