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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557060/
• 关键词: Multiple Sclerosis; Opticospinal form; SEREX; Autoantibody; HSP105; HLA-class II; 視神経脊髄型多発性硬化症; 自己抗原; HLAクラスII; SEREX法

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

多发性硬化症（MS）是目前假设介导的自身反应性T细胞对髓鞘抗原。在日本，MS经常和选择性地影响视神经和脊髓。我们以前曾报道，视脊髓型MS（OS-MS）已被证明是不同于传统形式的MS（C-MS）的临床，免疫学和免疫遗传学。最近，少突胶质细胞已被证明有多个来源，显示出显着的差异，分布取决于它们的起源。我们推测存在于视神经和脊髓中的特异性自身抗原可能与OS-MS病变的发生有关。我们利用从OS-MS患者获得的血清样品对人脊髓cDNA表达文库进行免疫筛选。用从8个OS-1中获得的血清对5个噬菌体噬斑进行免疫筛选。 ...更多信息 MS患者。通过对血清的反应性鉴定了11个阳性免疫反应克隆，并对其序列进行了分析。序列比较显示这些克隆代表来自5个不同基因（HSP 105、Rabaptin-5、NSD 1、KIAA 1640、KIAA 0640）的cDNA。我们制备了GST-Rabaptin-5融合蛋白和HSP 105蛋白，并采用ELISA法检测了血清和脑脊液中抗Rabaptin-5和抗HSP 105自身抗体的效价。我们发现IgG抗Rabaptin-5反应性没有显著升高，但MS患者的IgG抗HSP 105反应性显著高于正常对照组（p = 0.0193）。抗HSP 105抗体阳性率为3%（2/66），MS患者为14.5%（10/69）。在OS-MS和C-MS之间自身抗体的患病率差异无统计学意义。从9例MS患者中的3例建立了来源于CD 4 ^+ CD 45 RO ^+ T细胞的HSP 105 α反应性T细胞系，但未建立正常对照。我们的研究结果表明HSP 105是MS的一个新的候选自身抗原。在未来，我们将分析其他候选自身抗原（NSD 1，KIAA 1640，KIAA 0610）。少

项目成果

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Kira J: "A novel feature disclosed in opticospinal multiple sclerosis in Asians"Intern Med. 39. 272 (2000)

Kira J：“亚洲人视脊髓多发性硬化症的一个新特征”Intern Med。

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Osoegawa M, Matsumoto S, Ochi H, Ishiwata K, Nakamura-Uchiyama F, Nawa Y, Yamasaki K, Horiuchi I, Ohyagi Y, Kira J: "Localized myelitis caused by visceral larva migrans due to Ascaris suum masquerading as an isolated spinal cord tumor"J Neurol Neurosurg P

Osoekawa M、Matsumoto S、Ochi H、Ishiwata K、Nakamura-Uchiyama F、Nawa Y、Yamasaki K、Horiuchi I、Ohyagi Y、Kira J：“由于猪蛔虫伪装成孤立的脊髓，导致内脏幼虫移行症引起的局部脊髓炎

Nakatsura T, Senju S, Ito M, Nishimura Y^*, Itoh K.^* (^*equal contribution): "Cellular and Humoral Immune Responses to A Human Pancreatic Cancer Antigen, CLP, Originally Defined by the SEREX Method"Eur. J. Immunol.. (in press).

Nakatsura T、Senju S、Ito M、Nishimura Y^*、Itoh K.^*（^*同等贡献）：“对人类胰腺癌抗原 (CLP) 的细胞和体液免疫反应，最初由 SEREX 方法定义”Eur。