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

我们调查了多发性硬化症(MS)或慢性炎症性脱髓鞘多发性神经病(CIDP)患者中是否存在抗髓鞘抗体。应用酶联免疫吸附试验对90例MS患者和10例CIDP患者进行了抗髓鞘抗体的筛选。MS患者使用髓鞘少突胶质细胞糖蛋白(MOG)、髓鞘碱性蛋白(MBP)、蛋白脂蛋白(PLP)，CIDP患者使用PMP-22、PO糖蛋白(P0)、P2糖蛋白、连接蛋白-32。MS患者中，MOG抗体阳性2例，MBP抗体阳性4例，PLP抗体阳性5例。未观察到抗体滴度与临床严重程度之间的关系。相反，没有一名CIDP患者有针对外周髓鞘多肽的抗体。最后，我们不能提供抗体效价与MS的特征之间的证据。接下来，我们分析了与遗传性神经病和CIDP的关系。我们发现2例患者存在PO基因杂合点突变，其临床特征与CIDP相似。特别是1例PO基因杂合子Thr124Met点突变的老年女性，表现为双侧Adie‘s瞳孔、食道失弛缓症、低张肠、少汗和神经源性膀胱的轴索性神经病。她还在电生理上显示脱髓鞘神经病伴有颞叶弥散和传导阻滞，这是CIDP的典型表现。此外，在这位患者中，T细胞对PO多肽的反应性升高。本病例提示PO基因杂合性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而发生CIDP。

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.