Role of anti-endothelial cell antibodies and transendothelial migratory T cells in the pathogenesis of autoimmune lesions

抗内皮细胞抗体和跨内皮迁移T细胞在自身免疫病变发病机制中的作用

• 批准号: 06670495
• 负责人: KANO Shogo
• 金额: $ 1.54万
• 依托单位: Jichi medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670495/
• 关键词: Rheumatoid arthritis; Systemic lupus erythematosus; Ribosomal P0 protein; Transendothelial migration; Anti-endothelial cell antibody; Autoimmunity; T cells

Anti-endothelial cell antibody levels are elevated in sera from systemic lupus erythematosus (SLE) patients, especially in those who had pulmonary hypertension, digital vasculitis, Raynaud's phenomenon, or serositis. The antigens reacting with anti-endothelial cell antibodies is shown to be 36,37kD proteins by immunoblotting. The analysis of the cloned cDNA from human placenta cDNA library confirmed ribosomal P0 protein as the antigen. Enzyme-linked immunosorbent assay for anti-ribosomal P0 protein antibodies was established using recombinant fusion protein derived from cDNA as antigens. Anti-ribosomal P0 antibodies were positive only in sera from SLE patients, and positive anti-ribosomal P0 protein antibodies were correlated with central nervous system involvement other than lupus psychosis.Rheumatoid arthritis is characterized by chronic inflammation of synovium resulting in destruction of bone and cartilage of joints. Trans-endothelial migration of T cell subsets with surface phenotype of LFA-1 (intermediately positive), CD26 (highly positive) is involved in the pathogenesis of chronic synovitis. In vitro antigen-stimulated activation of those T cell subset is suppressed by disease-modifying anti-rheumatic drugs such as gold sodium thiomalate, auranofin or bucillamine. The greater level of suppression was observed in patients whoresponded the medication, indicating possible predicting value for these assessment

系统性红斑狼疮（SLE）患者血清中抗内皮细胞抗体水平升高，特别是在那些患有肺动脉高压、指血管炎、雷诺现象或浆膜炎的患者中。免疫印迹显示，与抗内皮细胞抗体反应的抗原为36，37 kD蛋白。对从人胎盘cDNA文库中克隆的cDNA进行分析，证实核糖体P0蛋白为抗原。以重组核糖体P0蛋白为抗原，建立了抗核糖体P0蛋白抗体的酶联免疫吸附试验。抗核糖体P0蛋白抗体仅在SLE患者血清中呈阳性，抗核糖体P0蛋白抗体阳性与中枢神经系统受累有关，而与狼疮性精神病无关。风湿性关节炎以滑膜慢性炎症导致关节骨和软骨破坏为特征。表面表型为LFA-1（中阳性）、CD 26（高阳性）的T细胞亚群的跨内皮迁移参与慢性滑膜炎的发病。这些T细胞亚群的体外抗原刺激活化被疾病修饰抗风湿药物如硫代苹果酸金钠、金诺芬或布西拉明抑制。在对药物有反应的患者中观察到更高水平的抑制，表明这些评估可能具有预测价值

项目成果

Yoshio T,et al.: "Antiribosomal P0 protein antibodies react with the surface of human umbilical vein endothelial cells." Journal of Rheumatology. (in press).

Yoshio T 等人：“抗核糖体 P0 蛋白抗体与人脐静脉内皮细胞表面发生反应。”

Yoshio T,Masuyama J,Sumiya M,Minato N,Kano S: "Antiendothelial cell antibodies and their relation to pulmonary hypertension in systmic lupus erythematosus." Journal of Rheumatology. 21. 2058-2063 (1994)

Yoshio T、Masuyama J、Sumiya M、Minato N、Kano S：“抗内皮细胞抗体及其与系统性红斑狼疮肺动脉高压的关系。”

Yoshio Y, et al.: "Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus." Annals of Rheumatic Disease. 54. 361-365 (1995)

Yoshio Y 等人：“系统性红斑狼疮患者血清诱导培养的内皮细胞释放内皮素 1。”

Yoshio T,Masuyama J,Ikeda M,Tamai K,Hachiya T,Emori T,Mimori A,Takeda A,Minota S,Kano S: "Quantification of antiribosomal P0 protein antibodies by ELISA with recombinant P0 fusion protein and their association with central nervous system disease in system

Yoshio T、Masuyama J、Ikeda M、Tamai K、Hachiya T、Emori T、Mimori A、Takeda A、Minota S、Kano S：“使用重组 P0 融合蛋白通过 ELISA 定量抗核糖体 P0 蛋白抗体及其与中枢神经的关联

Yoshio T.: "Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus" Ann Rheum Dis. 54. 361-365 (1995)

Yoshio T.：“系统性红斑狼疮患者血清诱导培养的内皮细胞释放内皮素 1”Ann Rheum Dis。