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Molecular cloning of autoantigens in rheumatoid arthritis

类风湿性关节炎自身抗原的分子克隆

基本信息

批准号：
08457152
负责人：
OZAKI Shoichi
金额：
$ 4.1万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

We cloned three cDNAs encoding autoantigens in rheumatoid arthritis (RA) by immunological screening of lambda phage synovial cell-cDNA libraries with synovial fluid IgG, both of which were derived from RA patients. One of the isolated cDNA clones was found to encode follistatin-related protein (FRP).ERP was first cloned as a transforming growth factor (TGF) beta1-inducible protein encoded by the TSC36 gene from a mouse osteoblastic cell line, and later human and rat homologues were cloned from glioma cell lines and named due to their similarity at the amino acid sequence level to follistatin (an inhibitor of activin), termed an FS module. FRP is a secreted extracellular soluble protein with unknown function. Immunoblotting analyzes detected serum antibodies to E.coli-expressed recombinant FRP in RA patients at a frequency of 30% (n=67), which was higher than those observed in any other systemic rheumatic diseases ; 10% (n=51) in systemic lupus erythematosus (P<0.01), 17% (n=18) in systemic sclerosis, 10% (n=10) in Sjogren's syndrome, and 0% (n=13) in polymyositis/dermatomyositis (P<0.05). Most of the epitopes were found within the EC domain. T cell antigenicity of FRP in RA patients remains to be examined. As follistatin specifically inhibits activin, FRP might inhibit or alter the growth factor-like activities of as yet unidentified ligands such as activin. It is therefore possible that antibodies to secreted soluble FRP might modify its function in the extracellular environment to exert some effect on the pathogenic process of RA.

我们通过使用滑液 IgG 对 lambda 噬菌体滑膜细胞 cDNA 文库进行免疫筛选，克隆了编码类风湿性关节炎 (RA) 自身抗原的 3 个 cDNA，这两种文库均来自 RA 患者。发现其中一个分离的 cDNA 克隆编码卵泡抑素相关蛋白 (FRP)。ERP 最初被克隆为由小鼠成骨细胞系的 TSC36 基因编码的转化生长因子 (TGF) β1 诱导蛋白，后来从胶质瘤细胞系中克隆出人类和大鼠同源物，并因其在氨基酸序列水平上与卵泡抑素相似而命名（激活素的抑制剂），称为 FS 模块。 FRP是一种分泌性细胞外可溶性蛋白，功能未知。免疫印迹分析在 RA 患者中检测到大肠杆菌表达的重组 FRP 的血清抗体，频率为 30% (n=67)，高于任何其他系统性风湿病中观察到的抗体；系统性红斑狼疮为 10% (n=51) (P<0.01)，系统性硬化症为 17% (n=18)，干燥综合征为 10% (n=10)，多发性肌炎/皮肌炎为 0% (n=13) (P<0.05)。大多数表位是在 EC 结构域内发现的。 RA 患者中 FRP 的 T 细胞抗原性仍有待研究。由于卵泡抑素特异性抑制激活素，FRP 可能会抑制或改变尚未鉴定的配体（例如激活素）的生长因子样活性。因此，分泌的可溶性 FRP 的抗体可能会改变其在细胞外环境中的功能，从而对 RA 的致病过程产生一些影响。