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神経免疫疾患における新規内在性レトロウイルスの検出とその病因的意義に関する研究

神经免疫性疾病中新型内源性逆转录病毒的检测及其致病意义研究

基本信息

批准号：
10670605
负责人：
HASHIMOTO Shiroshi
金额：
$ 1.98万
依托单位：
TOKYO WOMEN'S MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670605/
关键词：
multiple sclerosis retrovirus MSRV autoimmune disease

项目摘要

Multiple sclerosis is an autoimmune disease affecting primarily the central nervous system, whose etiologies has remained unknow. Perron et al have recently identified a novel human endogenous retrovirus (MSRV) in patients with multiple sclerosis (MS). We examined whether MSRV RNA can also be detected in Japanese MS patients. RNA was isolated from plasma of Japanese MS patients. After treatment with DNase I, RNA samples were used for RT-PCR which amplifes the pol region of MSRV. Genomic DNA, which was isolated from neutrophils, was used for PCR as control. PCR products were run on an agarose gel, transferred by Southern blotting and hybridized with the probe of MSRV pol region. The pol region of MSRV was amplified from genomic DNA by PCR from all the individuals tested. On the other hand, we could not amplify the MSRV sequence by RT-PCR, from plasma RNA samplesin in MS patients. Further studies are necessary to clarify the role of MSRV in the pathogenesis of multiple seclerosis in Japanese populations.On the other hand, during this study period, we revealed that the polymorphism at position 247 of the beta2-glycoprotein I gene is important for the generation of anti-beta2-glycoprotein I antibodies in the antiphospholipid syndrome, and that chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. These findings obtained in this study would be useful for better understanding of the pathogenesis of autoimmune diseases, including multiple sclerosis.

多发性硬化症是一种主要影响中枢神经系统的自身免疫性疾病，其病因尚不清楚。Perron等人最近在多发性硬化症（MS）患者中发现了一种新的人内源性逆转录病毒（MSRV）。我们研究了在日本MS患者中是否也可以检测到MSRV RNA。从日本MS患者的血浆中分离RNA。用DNase I处理后的RNA样品用于RT-PCR，其扩增MSRV的pol区。从嗜中性粒细胞中分离的基因组DNA用于PCR作为对照。PCR产物经琼脂糖凝胶电泳、Southern印迹转移后与MSRV pol区探针杂交。通过PCR从所有测试个体的基因组DNA扩增MSRV的pol区域。另一方面，我们不能用RT-PCR从MS患者的血浆RNA样品中扩增MSRV序列。需要进一步的研究来阐明MSRV在日本人群中多发性分泌物的发病机制中的作用。另一方面，在本研究期间，我们发现β 2-糖蛋白I基因247位的多态性对于抗磷脂综合征中抗β 2-糖蛋白I抗体的产生很重要，以及慢性淋巴细胞白血病B细胞表达突变和未突变抗原受体的限制性集合。本研究的这些发现将有助于更好地了解自身免疫性疾病，包括多发性硬化症的发病机制。