Molecular cloning of autoantigens in rheumatoid arthritis

我们从类风湿关节炎(RA)患者的滑膜细胞中克隆了3个编码自身抗原的c DNA片段。其中一个克隆编码卵泡抑素相关蛋白(FRP)，首先从小鼠成骨细胞系中克隆出由TSC36基因编码的转化生长因子β1诱导蛋白，然后从胶质瘤细胞系中克隆了人和大鼠的同源物，因为它们在氨基酸水平上与激活素的抑制物卵泡抑素相似而命名为FS模块。FRP是一种功能未知的分泌型胞外可溶性蛋白。免疫印迹分析检测到的血清抗体在RA患者中为30%(n=67)，高于其他系统性风湿性疾病，在系统性红斑狼疮(P&lt；0.01)中为10%(n=51)，在系统性硬化症中为17%(n=18)，在干燥综合征中为10%(n=10)，在多发性肌炎/皮肌炎中为0(P&lt；0.05)。大部分表位位于EC结构域内。RA患者外周血中FRP的T细胞抗原性有待进一步研究。由于卵泡抑素特异性地抑制激活素，FRP可能抑制或改变诸如激活素等尚未确定的配体的生长因子样活性。因此，分泌可溶性FRP的抗体可能会改变其在细胞外环境中的功能，从而对RA的发病过程产生一定的影响。

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.