权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular biological study＼ies in a novel peripheral nerve myelin protein and its application to clinical neurology

新型周围神经髓鞘蛋白的分子生物学研究及其在临床神经病学中的应用

基本信息

批准号：
09670643
负责人：
FURUKAWA Tetsuo
金额：
$ 1.47万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

We tried to characterize a 35-kd antigen recognized by the serum IgG of a patient with malignant lymphoma and peripheral neuropathy. On western blotting, the serum IgG reacted with a 35-kd antigen in human, bovine and mouse peripheral nerves (PN) but not with other neural and non-neural tissues. Immunohistochemical analysis showed immunoreactivity for the IgG in the compact myelin of PN. We constructed a human sciatic nerve cDNA library and screened it using the patient's IgG. We identified three independent clones. A homology search of the inserts of these clones revealed that the inserts were homologous to P0 cDNA. However, all the inserts corresponded to the 3'-untranslational region of P0 cDNA. Then, to analyze the 35-kd antigen biochmically, myelin fractions of human and bovine sciatic nerve were prepared. Using SDS-polyacrylamide gel electrophresis, the 35-kd antigen was purified from the crude myelin fraction. When the immunoreactivities of the 35-kd antigen for the patient's IgG and monoclonal anti-P0 antibody were compared with those of protein P0 for these antibodies, the 35-kd antigen reacted with both the antibodies, but P0 reacted with only monoclonal anti-P0 antibody. These results indicate the possibility of the 35-kd antigen being an isoform of P0. However, the presence of these autoantibodies against the 35-kd antigen seems to be of little pathological significance, because circulating autoantibodies against the antigen were also found in the sera of patients with malignant lymphoma without associated peripheral neuropathy.

我们试图表征恶性淋巴瘤和周围神经病患者血清 IgG 识别的 35-kd 抗原。在蛋白质印迹中，血清 IgG 与人、牛和小鼠周围神经 (PN) 中的 35 kd 抗原发生反应，但不与其他神经和非神经组织发生反应。免疫组织化学分析显示 PN 致密髓磷脂中的 IgG 具有免疫反应性。我们构建了人类坐骨神经 cDNA 文库，并使用患者的 IgG 对其进行了筛选。我们鉴定了三个独立的克隆。对这些克隆的插入片段进行同源性搜索表明，插入片段与 P0 cDNA 同源。然而，所有插入片段均对应于 P0 cDNA 的 3'-非翻译区。然后，为了对 35-kd 抗原进行生物化学分析，制备了人和牛坐骨神经的髓磷脂部分。使用 SDS 聚丙烯酰胺凝胶电泳，从粗髓磷脂部分中纯化出 35-kd 抗原。当将患者 IgG 和单克隆抗 P0 抗体的 35-kd 抗原的免疫反应性与这些抗体的蛋白 P0 的免疫反应性进行比较时，35-kd 抗原与两种抗体都发生反应，但 P0 仅与单克隆抗-P0 抗体发生反应。这些结果表明 35-kd 抗原可能是 P0 的同种型。然而，这些针对 35-kd 抗原的自身抗体的存在似乎没有什么病理意义，因为在没有相关周围神经病变的恶性淋巴瘤患者的血清中也发现了针对该抗原的循环自身抗体。