Yamawaki M, Vasquez A, Ben Younes A, Yoshino H, Kanda T, Ariga T, Baumann N, Yu R K
Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0614, USA.
J Neurosci Res. 1996 Apr 1;44(1):58-65. doi: 10.1002/(SICI)1097-4547(19960401)44:1<58::AID-JNR8>3.0.CO;2-H.
Antibodies against sulfoglucuronosyl glycosphingolipids (SGGLs) are known to be present in sera of patients with chronic polyneuropathy associated with IgM paraproteinemia. We recently studied rats sensitized with sulfoglucuronosyl paragloboside (SGPG), a major SGGL species, emulsified with keyhold limpet hemocyanin and Freund's adjuvant. The titer of the IgM class antibodies against SGPG increased up to 1:1,600, while that of the IgG class increased up to 1:800 2 weeks after sensitization. The antibodies showed a high degree of antigenic specificity; no cross-reactivity with other brain glycolipids could be detected. They, however, reacted with human myelin-associated glycoprotein (MAG) by Western blot analysis, but not with rat MAG. These animal models showed minor but clear clinical signs of neuropathy, consisting of mild tail muscle tone loss and walking disabilities. Electrophysiological examination of the sciatic nerves revealed nerve conduction abnormalities which consisted of conduction block and mild decrease in conduction velocity. Thus, our results support the concept that anti-SGPG antibodies may play an important pathogenetic role in this type of chronic neuropathy.
已知抗磺基葡糖醛酸糖鞘脂(SGGLs)抗体存在于与IgM副蛋白血症相关的慢性多发性神经病患者的血清中。我们最近研究了用磺基葡糖醛酸副球蛋白(SGPG,一种主要的SGGL种类)与钥孔戚血蓝蛋白和弗氏佐剂乳化后致敏的大鼠。致敏2周后,抗SGPG的IgM类抗体效价升至1:1600,而IgG类抗体效价升至1:800。这些抗体表现出高度的抗原特异性;未检测到与其他脑糖脂的交叉反应性。然而,通过蛋白质印迹分析,它们与人髓鞘相关糖蛋白(MAG)发生反应,但与大鼠MAG不发生反应。这些动物模型表现出轻微但明显的神经病临床症状,包括轻度尾肌张力丧失和行走障碍。对坐骨神经的电生理检查显示神经传导异常,包括传导阻滞和传导速度轻度降低。因此,我们的结果支持抗SGPG抗体可能在这类慢性神经病中起重要致病作用这一概念。