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

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类内源性逆转录病毒(MSRV)。我们检查了在日本多发性硬化症患者中是否也能检测到MSRV RNA。从日本多发性硬化症患者血浆中提取RNA。RNA样品经DNase I处理后，进行RT-PCR，扩增MSRV的Pol1区。以从中性粒细胞中提取的基因组DNA作为对照。聚合酶链式反应产物在琼脂糖凝胶上，经Southern blotting转移后，与MSRV Pol1区的探针杂交。从所有供试个体的基因组DNA中均扩增出MSRV的Pol区。另一方面，我们不能用RT-PCR从MS患者的血浆RNA中扩增出MSRV序列。另一方面，在本研究期间，我们揭示了β2-糖蛋白I基因第247位的多态性对抗磷脂综合征中抗β2-糖蛋白I抗体的产生起重要作用，慢性淋巴细胞白血病B细胞表达有限的突变和未突变的抗原受体。这些发现将有助于更好地理解包括多发性硬化症在内的自身免疫性疾病的发病机制。

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.