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The analysis of genetic abnormality of the target molecule in neuroimmunological disease

神经免疫疾病靶分子基因异常分析

基本信息

批准号：
17590905
负责人：
MIYAMOTO Katsuichi
金额：
$ 2.24万
依托单位：
Kinki Univeristy
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590905/
关键词：
Brain, Nerve Peripheral Nerve Gene Immunology Auto antibody 抹消神経

项目摘要

We investigated whether the anti-myelin antibody is present in multiple sclerosis (MS) or chronic inflammatory demyelinating polyneuropathy (CIDP) patients. We screened anti-myelin antibody in the sera of 90 MS patients and 10 CIDP patients by ELISA. We used peptides of myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), proteolipid protein (PLP) for MS patients, and PMP-22, PO glycoprotein (P0), P2 glycoprotein, Connexin-32 for CIDP patients. As for MS, 2 patients were seropositive for IgG antibody to MOG, 4 patients for IgG antibody to MBP, and 5 patients for IgG antibody to PLP. No relation between antibody titer and clinical severity was observed. In contrast, no CIDP patients had antibodies agains peripheral myelin peptides. Finally we could not provide evidence between the titer of the antibody and the character of MS.Next, we analyzed the relationship with hereditary neuropathy and CIDP. We found two patients that they have heterozygous point mutation in the PO gene with similar clinical characters similar to CIDP. Especially an elderly woman with the heterozygous Thr124Met point mutation in the PO gene presented an axonal neuropathy with bilateral Adie's pupils, esophageal achalasia, hypotonic intestine, hypohidrosis and neurogenic bladder. She also showed demyelinating neuropathy with temporal dispersions and conduction blocks electrophysiolosically, which is typical of CIDP. In addition, reactivity of T cells against PO-peptides was elevated in this patient. This case indicated that the heterozygous PO gene mutation itself could induce auto-immunological reaction to develop CIDP through T cell activation against PO-protein.

我们研究了抗髓鞘抗体是否存在于多发性硬化症（MS）或慢性炎症性脱髓鞘性多发性神经病（CIDP）患者。用ELISA法对90例MS患者和10例CIDP患者血清中抗髓鞘抗体进行了检测。对MS患者采用髓鞘少突胶质细胞糖蛋白（MOG）、髓鞘碱性蛋白（MBP）、蛋白脂质蛋白（PLP）的多肽;对CIDP患者采用PMP-22、PO糖蛋白（P0）、P2糖蛋白、连接蛋白-32的多肽。对于MS，2例患者血清MOG IgG抗体阳性，4例患者血清MBP IgG抗体阳性，5例患者血清PLP IgG抗体阳性。未观察到抗体滴度与临床严重程度之间的关系。相反，没有CIDP患者有抗外周髓鞘肽的抗体。最后，我们不能提供抗体滴度与MS的特征之间的证据。接下来，我们分析了遗传性神经病和CIDP的关系。发现2例PO基因杂合性点突变患者，其临床特征与CIDP相似。特别是一位在PO基因中有杂合子Thr 124 Met点突变的老年女性，表现为轴突神经病变，伴有双侧Adie瞳孔、食管失弛缓症、低张力肠、少汗和神经源性膀胱。她还表现出脱髓鞘性神经病伴时间离散和电生理传导阻滞，这是典型的CIDP。此外，T细胞对PO-肽的反应性在该患者中升高。该病例表明，杂合PO基因突变本身可通过激活T细胞对抗PO蛋白而诱导自身免疫反应发展为CIDP。