Effect of autoantihody from myasthenia gravis and immunosuppressant on gene expression of skeletal muscle

重症肌无力自身抗体与免疫抑制剂对骨骼肌基因表达的影响

• 批准号: 16590818
• 负责人: YOSHIKAWA Hiroaki
• 金额: $ 1.66万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590818/
• 关键词: Myasthenia gravis; Thymus; Thymoma; Interleukin -12; Autoantihndies; 抗サイトカイン抗体; IL-12 p40; IL-12 p70; IL-12p40; IL-12p70; アセチルコリン受容体; 細胞内カルシウム; リアノジン受容体; IP3受容体; FK506; 横紋筋; 平滑筋

Myasthenia gravis (MG) is thought to be a disorder targeting at the acetylcholine receptor (AChR) on postsynaptic membrane of neuromuscular junction (NMJ). One of clinical characteristics of MG is high prevalence of thymic abnormality as high as 90% of patients. About 80% of patients have thymic follicular hyperplasia and 20% have thymoma. The patients with thymoma are refractory to therapy, i.e., they need to receive high amount of steroid for treatment. We measured AChR antibody, cytokines and antibodies against cytokines for studying the autoimmunity of MG patients with thymoma. For measurement of AChR antibodies, we used immunoprecipitation method. For measurement of cytokines, enzyme-linked immunosorbent assay (ELISA) was applied. For measurement of antibodies against cytokines, the modified ELISA was utilized. As a result, antibodies against interleukin (IL)-12 p70 were high in patients with thymoma with or without MG. IL-12 p40 and anti-IL-12 p40 antibodies elevated in sera from MG patients with thymoma. Additionally, we developed assay system for detecting antibodies against ryanodine receptor (RyR) that have a role in excitation-contraction (E-C) coupling of skeletal muscle. The method use whole protein of RyR instead to synthetic peptide, and is more sensitive and specific than ELISA system using synthetic peptide. Using detection system for RyR antibodies, we found that a group of MG patients with thymoma have autoantibodies against both AChR and RyR. Therefore, the pathological targets of MG patients with thymoma are synaptic transmission (AChR) and E-C coupling (RyR).

肌无力被认为是针对乙酰胆碱受体（ACHR）的一种疾病，该疾病是在神经肌肉结（NMJ）的突触后膜上的疾病。 MG的临床特征之一是胸腺异常高达90％的患者。约80％的患者患有胸腺卵泡增生，20％患有胸腺瘤。胸腺瘤患者对治疗是难治性的，即，他们需要接受大量类固醇进行治疗。我们测量了针对细胞因子的ACHR抗体，细胞因子和抗体，用于研究MG胸腺瘤患者的自身免疫性。为了测量ACHR抗体，我们使用了免疫沉淀法。为了测量细胞因子，应用了酶连接的免疫吸附测定法（ELISA）。为了测量针对细胞因子的抗体，使用了修饰的ELISA。结果，针对白介素（IL）-12 p70的抗体在患有或没有mg的胸腺瘤患者中很高。 MG胸腺瘤患者的血清中升高的IL-12 p40和抗IL-12 p40抗体。此外，我们开发了用于检测抗ryanodine受体（RYR）抗体的测定系统，该抗体在骨骼肌的激发诱导（E-C）偶联中起作用。该方法使用RYR的全蛋白代替合成肽，并且比使用合成肽更敏感和特异性。使用RYR抗体的检测系统，我们发现一组胸腺瘤患者具有对ACHR和RYR的自身抗体。因此，胸腺瘤患者的病理靶标是突触传播（ACHR）和E-C偶联（RYR）。

项目成果

IL-12 p40 and its antibody are specific marker for myasthenia gravis with thymoma. Comparative study with IL-12 p70 antibody and ryanodine receptor antibody. New Treatment Strategy of Myasthenia Gravis Basic researches and Clinical experiences of Tacrolim

IL-12 p40及其抗体是胸腺瘤重症肌无力的特异性标志物。

• 发表时间: 2006
• 作者: Yoshikawa;H
• 通讯作者: H

IL-12 p40 and its antibody are specific marker for myasthenia gravis with thymoma. Comparative study with IL-12 p70 antibody and ryanodine receptor antibody. New Treatment Strategy of Myasthenia Gravis-Basic researches and Clinical experiences of Tacrolim

IL-12 p40及其抗体是胸腺瘤重症肌无力的特异性标志物。

• 发表时间: 2006
• 作者: Kazuhiro Nakaso;et al.;Hiroaki Yoshikawa
• 通讯作者: Hiroaki Yoshikawa

Autoantibodies against M1 muscarinic acetylcholine receptor in myasthenic syndrome□.

肌无力综合征中针对 M1 毒蕈碱乙酰胆碱受体的自身抗体□。

• 发表时间: 2007
• 期刊: Eur J Neurol 14
• 作者: Masaharu Takamori;et. al.
• 通讯作者: et. al.

重症筋無力症における患者年齢層の変遷と胸腺組織について.

重症肌无力患者年龄组和胸腺组织的变化。

• 发表时间: 2004
• 期刊: 神経免疫学 12
• 作者: 岩佐和夫;他
• 通讯作者: 他

重症筋無力症末梢血単核球のサイトカイン産生に対する免疫抑制薬の影響

免疫抑制剂对重症肌无力外周血单个核细胞细胞因子产生的影响

• 发表时间: 2006
• 作者: 古川 裕;他
• 通讯作者: 他