Nickowitz R E, Worman H J
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
J Exp Med. 1993 Dec 1;178(6):2237-42. doi: 10.1084/jem.178.6.2237.
Patients with primary biliary cirrhosis (PBC) frequently have autoantibodies against a 210-kD integral glycoprotein of the nuclear envelope pore membrane. This protein, termed gp210, has a 1,783-amino acid amino-terminal domain located in the perinuclear space, a 20-amino acid transmembrane segment, and a 58-amino acid cytoplasmic carboxy-terminal tail. We now demonstrate that autoantibodies from 25 patients with PBC that recognize gp210 react with the cytoplasmic carboxy-terminal tail while none react with unmodified linear epitopes in the amino-terminal domain. The epitope(s) recognized by autoantibodies from all 25 patients is contained within a stretch of 15 amino acids. The recognized amino acid sequence is homologous to the protein products of the Escherichia coli mutY gene and Salmonella typhimurium mutB gene with an exact identity of six consecutive amino acids, suggesting that anti-gp210 antibodies may arise by molecular mimicry of bacterial antigenic determinants.
原发性胆汁性肝硬化（PBC）患者常常具有针对核被膜孔膜一种210-kD整合糖蛋白的自身抗体。这种蛋白，称为gp210，具有位于核周间隙的1783个氨基酸的氨基末端结构域、一个20个氨基酸的跨膜区段以及一个58个氨基酸的细胞质羧基末端尾巴。我们现在证明，来自25例识别gp210的PBC患者的自身抗体与细胞质羧基末端尾巴发生反应，而没有一个与氨基末端结构域中未修饰的线性表位发生反应。所有25例患者的自身抗体识别的表位包含在一段15个氨基酸中。所识别的氨基酸序列与大肠杆菌mutY基因和鼠伤寒沙门氏菌mutB基因的蛋白产物同源，有六个连续氨基酸完全相同，这表明抗gp210抗体可能通过细菌抗原决定簇的分子模拟而产生。
