Identification and localization of minor glycolipid antigens recognized by serum antibody in Guillain-Barre' syndrome

格林-巴利综合征血清抗体识别的次要糖脂抗原的鉴定和定位

• 批准号: 05670551
• 负责人: KUSUNOKI Susumu
• 金额: $ 1.34万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670551/
• 关键词: Guillain-Barre' syndrome; Ganglioside; Glycolipid; Galactocerebroside; Mycoplasma pneumoniae; Myelin; Demyelination; Neuropathy; フィッシャー症候群; GQ1b; GM1; シァリダーゼ; GalNAc-GD1a; GQ16; GD16

Because of the effectiveness of plasmapheresis, humoral factors including autoantibodies may function in the pathogenetic process of Guillain-Barre' syndrome (GBS). Serum antibodies against several glycolipids have been reported in patients in the acute phase sera of GBS,their titers decreasing with clinical improvement. Because minor unidentified glycolipids also may be targets of antibodies in GBS sera, we assayd serum antibody against a crude ganglioside fraction using thin-layr chromatogram (TLC) immunostaining. Antibody activity was detected against a band that migrated just below GD1a in 6 of the 50 patients with GBS tested. The unidentified glycolipid was isolated by DEAE-Sephadex A-25 column chromatography, sialidase treatment, and Iatrobeads column chromatography. Fast atom bombardment-mass spectra showed it to be GalNAc-GD1a. All 6 patients had suffered gastrointestinal infection before the neurological onset of GBS and showed low amplitudes for the compound muscle action pot … More entials and normal or only slightly decreased nerve conduction velocities. Therefore, this antibody may be raised in GBS with axonal damage or demyelinative change in the most distal sites of the peripheral nerve. Future study is necessary for determining localization of GalNAc-GD1a. Mycoplasma pneumoniae is one agent of the infections preceding GBS.Four of 82 patients with GBS suffered from mycoplasma infection before onset of GBS.All four patients had antibody against galactocerebroside (Gal-C). Two of 78 patients with GBS without mycoplasma infection had anti-Gal-C antibody but none of the disease or normal controls had it. Thus anti-Gal-C antibody may be characteristically raised in GBS subsequent to mycoplasma infection. Gal-C is known to be an important antigen in myelin, and sensitization to Gal-C has been reported to cause antibody-mediated demyelinative neuropathy in rabbit. The anti-Gal-C antibodies may function in the pathophysiologic mechanism of demyelinative neuropathy in patients with GBS subsequent to mycoplasma infection. Less

由于血浆置换的有效性，包括自身抗体在内的体液因子可能在格林-巴利综合征（GBS）的发病过程中起作用。据报道，GBS急性期患者血清中存在几种糖脂抗体，其滴度随临床改善而降低。由于少量未确定的糖脂也可能是GBS血清中抗体的靶点，我们使用薄层色谱（TLC）免疫染色法检测了针对粗神经节苷脂部分的血清抗体。在50例GBS患者中，有6例检测到抗体活性针对迁移到GD1a下方的条带。采用DEAE-Sephadex A-25柱层析、唾液酸酶处理和Iatrobeads柱层析分离得到未确定的糖脂。快速原子轰击-质谱分析表明其为GalNAc-GD1a。6例患者在GBS神经学发病前均有胃肠道感染，复合肌动作波呈低振幅，神经传导速度正常或仅轻微下降。因此，这种抗体可能在周围神经最远端轴突损伤或脱髓鞘改变的GBS中升高。GalNAc-GD1a的定位需要进一步的研究。肺炎支原体是GBS之前感染的一种病原体。82例GBS患者中有4例在发病前曾发生支原体感染。4例患者均有半乳糖脑苷（Gal-C）抗体。78例无支原体感染的GBS患者中有2例有抗gal - c抗体，但患者和正常对照均无。因此，在支原体感染后的GBS中，抗gal - c抗体可能特征性地升高。已知Gal-C是髓磷脂中的重要抗原，有报道称，Gal-C致敏可引起兔抗体介导的脱髓鞘性神经病变。抗gal - c抗体可能在支原体感染后GBS患者脱髓鞘性神经病变的病理生理机制中起作用。少

项目成果

Kusunoki S,et al.: "Localization of GM1 and GD1b antigens in the human peripheral nervous system." Muscle & Nerve. 16. 752-756 (1993)

Kusunoki S 等人：“GM1 和 GD1b 抗原在人类周围神经系统中的定位”。

Arasaki K,et al.: "Acute conduction block in vitro following exposure to antiganglioside sera." Muscle & Nerve. 16. 587-593 (1993)

Arasaki K 等人：“暴露于抗神经节苷脂血清后体外急性传导阻滞。”

Kusunoki S, et al.: "Localization of GM1 and GD1b antigents in the human peripheral nervous system" Muscle & Nerve. 16. 752-756 (1993)

Kusunoki S 等人：“GM1 和 GD1b 抗原在人类周围神经系统中的定位”肌肉

Nishiyama K,et al: "Carcinomatous neuropathy associated with hepatic cell carcinoma:an autopsy case report" Neuromuscular Disorders. 3. 227-229 (1993)

Nishiyama K 等人：“与肝细胞癌相关的癌性神经病：尸检病例报告”神经肌肉疾病。

Kusunoki S,et al.: "N-acetylgalactosaminyl GD1a is a target molecule for serum antibody in Guillain-Barre' syndrome." Annals of Neurology. 35. 570-576 (1994)

Kusunoki S 等人：“N-乙酰半乳糖胺基 GD1a 是格林-巴利综合征血清抗体的靶分子。”