Identification of a specific autoantigen in opticospinal form of multiple sclerosis based on the HLA-DPB1 binding motif

基于 HLA-DPB1 结合基序鉴定多发性硬化症视脊髓形式的特异性自身抗原

基本信息

批准号：
12557060
负责人：
KIRA Jun-ichi
金额：
$ 8.64万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Multiple sclerosis (MS) is currently hypothesized to be mediated by autoreactive T cells against myelin antigens. In Japanese, MS frequently and selectively affects the optic nerve and spinal cord. We have previously reported that the opticospinal form of MS (OS-MS) has been shown to be distinct from the conventional form of MS (C-MS) clinically, immunologically and immunogenetically. Recently, oligodendrocytes have been demonstrated to have plural origins, showing marked differences in distribution depending on their origin. We assumed that the specific autoantigens which exist in the optic nerve and spinal cord may be associated with development of OS-MS lesions.To identify the autoantigens in OS-MS, we made use of an immunoscreening of a human spinal cord cDNA expression library with serum samples obtained from patients with OS-MS. cDNA expression library was prepared from human spinal cord and 5 X 10^5 to 10 X 10^5 phage plaques were immunoscreened with sera obtained from eight OS- … More MS patients. Eleven positive immunoreactive clones were identified by their reactivity to the sera, and their sequences were analyzed. Comparisons of the sequences showed that these clones represented cDNAs from 5 distinct genes (HSP105, Rabaptin-5, NSD1, KIAA1640, KIAA0640). We produced GST-Rabaptin-5 fusion protein and HSP105 protein and evaluated the titer of IgG anti-Rabaptin-5 and anti-HSP105 autoantibody in sera and CSF, using ELISA. We found IgG anti-Rabaptin-5 reactivities were not significantly elevated, however IgG anti-HSP105 reactivities in MS patients was significantly higher than those in normal controls (p = 0.0193). Anti-HSP105 reactivities were found in 3 % (2/66) of normal controls, while 14.5 % (10/69) of patients with MS were positive for anti-HSP105 antibodies. The difference in prevalence of autoantibodies was not statistically significant between OS-MS and C-MS. The HSP105 α-reactive T cell lines derived from CD4^+CD45RO^+ T cells were established from 3 of 9 MS patients but not normal controls. Our findings indicate HSP105 to be a novel candidate autoantigen in MS. In future, we are going to analyze the other candidate autoantigens (NSD1, KIAA1640, KIAA0610). Less

当前，多发性硬化症（MS）是由自身反应性T细胞针对髓磷脂抗原介导的。 MS（C-MS）在临床上，免疫学和无义构，少突胶质细胞被证明具有复数的起源，显示出其起源，这是在视神经伴侣Mays中使用人类脊髓丝cDNA表达式库中的。 OS -MS的患者。分析了这些克隆来自5种不同基因的克隆（HSP105，Rab。Aptin-5，NSD1，KIAA1640，KIAA0640）血清和CSF中的自身抗体显着升高，但是MS患者的IgG抗HSP105反应率明显高于在3％（2/66）正常对照组中发现的Inti-HSP105激活性，而14.5％（10/69）抗HSP105抗体的阳性是自身抗体的患病率在OS-MS和C-MS之间的统计学意义HSP105将在未来的女士中进行自动抗原