Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis

✍ Scribed by O Bandin; J Courvalin; R Poupon; L Dubel; J Homberg; C Johanet

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 172 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230512

✦ Synopsis

Between 10% and 42% of patients with primary biliary a critical tool for the diagnosis of PBC. Approximately cirrhosis (PBC) have been reported to have autoantibod-95% of patients with PBC have antibodies against a ies directed against a restricted epitope of gp210, a glycofamily of mitochondrial autoantigens, in particular the protein of the nuclear pore membrane. The prevalence three subunits of the ketoacid dehydrogenase comand specificity of these antibodies was studied in a plexes. However, antimitochondrial antibodies French series of 285 patients with PBC and 497 control (AMA) of other specificities are sometimes observed in individuals affected with other liver or autoimmune dispatients with other autoimmune diseases, 7,8 whereas a eases. Sera were analyzed by an enzyme-linked immunofew patients with PBC do not have AMA. sorbent assay (ELISA) that used a synthetic polypeptide Other families of antibodies, including several types containing the predominant autoepitope of gp210, in of antinuclear autoantibodies (ANA), have been obparallel to immunoblotting of gp210 protein and immunofluorescence microscopy. Autoantibodies to the gp210 served in PBC that can be helpful in the diagnosis of epitope detected by ELISA were 25.5% sensitive and this disease. A subset of PBC patients (28%-52%) have 99.5% specific for the diagnosis of PBC. These results antibodies that stain the periphery of the nucleus by were in agreement with a 99.4% specificity with immuindirect immunofluorescence microscopy. [12][15] The annoblotting analysis and a 96.6% specificity with immunotigens have been identified as proteins of the nuclear fluorescence. In a subset of PBC patients without detectenvelope. 16 Some of these antibodies recognize the nuable antimitochondrial autoantibodies (AMA), gp210 clear lamins, 10 although anti-lamin antibodies are autoantibodies were found in 7 of 15 patients (47%). more commonly found in patients with systemic lupus Therefore, gp210 autoantibodies are highly specific for erythematosus 17 and autoimmune hepatitis. 18,19 A few PBC and may be of particular utility in assessing papatients with PBC also have antibodies that react with tients without AMA or with other atypical presentations. (HEPATOLOGY 1996;23:1020-1024.) the lamin B receptor, 15 an integral protein of the inner nuclear membrane. 20, The most frequent target of autoantibodies directed Primary biliary cirrhosis (PBC) is a chronic choleagainst the nuclear envelope in patients with PBC is static liver disease characterized by nonsuppurative in-gp210, a glycoprotein of 210 kd that is located at the flammatory destruction of small bile ducts that leads nuclear pore. Ten percent to 42% of patients with to cirrhosis. In combination with clinical, biochemi-PBC have been shown to have antibodies directed cal, and histological criteria, autoantibody detection is against this protein. [15] Studies using a variety of methods, including immunoblotting assays of nuclear envelope proteins or recombinant polypeptides [15] and, Abbreviations: PBC, primary biliary cirrhosis; AMA, antimitochondrial anmore recently, an enzyme-linked immunosorbent assay tibodies; ANA, antinuclear antibodies; ELISA, enzyme-linked immunosorbent (ELISA) using a bacterial fusion protein, 26 have estabassay; PBS, phosphate-buffered saline; SDS, sodium dodecyl sulfate.