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

我们研究了抗髓磷脂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神经病变（CIDP）患者中。采用ELISA法对90例MS患者和10例CIDP患者血清中抗髓磷脂抗体进行筛选。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）多肽，CIDP患者采用PMP-22、PO糖蛋白（P0）、P2糖蛋白、Connexin-32多肽。MS血清MOG IgG抗体阳性2例，MBP IgG抗体阳性4例，PLP IgG抗体阳性5例。抗体滴度与临床严重程度无相关性。相比之下，没有CIDP患者有针对外周髓磷脂肽的抗体。最后，我们无法提供抗体滴度与ms特征之间的证据。接下来，我们分析了与遗传性神经病变和CIDP的关系。我们发现2例患者PO基因杂合点突变，临床特征与CIDP相似。特别是PO基因杂合Thr124Met点突变的老年妇女，表现为双侧Adie's瞳孔轴突神经病，食管贲门失弛缓症，低渗肠，少汗和神经源性膀胱。她还表现出脱髓鞘神经病变，伴有颞叶弥散和电生理上的传导阻滞，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。本病例提示PO基因杂合突变本身可通过T细胞活化PO蛋白诱导自身免疫反应发生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.