Kamakura Keiko, Kaida Ken-ichi, Kusunoki Susumu, Miyamoto Norikazu, Masaki Toshihiro, Nakamura Ryohji, Motoyoshi Kazuo, Fukuda Jun
Third Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
J Peripher Nerv Syst. 2005 Jun;10(2):190-201. doi: 10.1111/j.1085-9489.2005.0010209.x.
The clinical characteristics of five (22%) of 23 patients with Guillain-Barré syndrome (GBS), whose serum contained immunoglobulin G (IgG) antibodies to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a), included pure motor weakness of the axonal type. These patients had a relatively good prognosis, but displayed higher serum tumor necrosis factor-alpha (TNF-alpha) titers than the other GBS patients. We examined the effect of serum from these patients with IgG anti-GalNAc-GD1a antibodies on neurites from cultured rat dorsal root ganglia (DRG) and found it to damage the myelin in well-elongated DRG neurites and monolayer cultures of Schwann cells and neurons. In the regeneration model, serum from these patients delayed neurite extension and inhibited Schwann cell proliferation. Neurons in cultured monolayers showed vacuolation and decreased rapidly in number. Schwann cells were also vacuolated and readily detached from the substratum. The effects of IgG anti-GalNAc-GD1a antibodies purified from one of the patients, rabbit serum after immunization with GalNAc-GD1a, and recombinant TNF-alpha were also examined. IgG anti-GalNAc-GD1a antibodies mainly inhibited the regeneration and preservation of neurons, while TNF-alpha mainly induced morphological changes in well-proliferated Schwann cells and myelin.
23例吉兰-巴雷综合征（GBS）患者中有5例（22%）血清中含有针对神经节苷脂N-乙酰半乳糖胺基GD1a（GalNAc-GD1a）的免疫球蛋白G（IgG）抗体，其临床特征包括轴索性单纯运动性肌无力。这些患者预后相对较好，但血清肿瘤坏死因子-α（TNF-α）滴度高于其他GBS患者。我们检测了这些含IgG抗GalNAc-GD1a抗体患者的血清对培养的大鼠背根神经节（DRG）神经突的影响，发现其会损伤生长良好的DRG神经突以及雪旺细胞和神经元单层培养物中的髓鞘。在再生模型中，这些患者的血清会延迟神经突延伸并抑制雪旺细胞增殖。培养单层中的神经元出现空泡化且数量迅速减少。雪旺细胞也出现空泡化并容易从基质上脱落。我们还检测了从其中1例患者纯化的IgG抗GalNAc-GD1a抗体、用GalNAc-GD1a免疫后的兔血清以及重组TNF-α的作用。IgG抗GalNAc-GD1a抗体主要抑制神经元的再生和存活，而TNF-α主要诱导增殖良好的雪旺细胞和髓鞘发生形态学改变。
