权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

我们克隆了3个编码类风湿关节炎（RA）自身抗原的cDNA的免疫筛选λ噬菌体滑膜细胞的cDNA文库与滑液IgG，这两个都来自RA患者。其中一个cDNA克隆被发现编码卵泡抑素相关蛋白（follistatin-related protein，FRP），ERP最初是从小鼠成骨细胞系中克隆的由TSC 36基因编码的转化生长因子（transforming growth factor，TGF）β 1诱导的蛋白，后来从胶质瘤细胞系中克隆了人和大鼠的同源物，并由于它们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是一种分泌型胞外可溶性蛋白，功能尚不清楚。免疫印迹分析检测到RA患者血清中抗大肠杆菌表达的重组FRP抗体的频率为30%（n=67），高于任何其他全身性风湿性疾病中观察到的抗体;系统性红斑狼疮10%（n=51）系统性硬化症18例，干燥综合征10例，多发性肌炎/皮肌炎13例，阳性率分别为17%（n=18）、10%（n=10）和0%（n=13）（P<0.05）。大多数表位被发现在EC结构域内。RA患者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可能抑制或改变尚未鉴定的配体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的致病过程产生一定的影响。