PBC Screen: An IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis

• Published in: Journal of autoimmunity Vol. 35; no. 4; pp. 436 - 442
• Main Authors: Liu, Haiying, Norman, Gary L, Shums, Zakera, Worman, Howard J, Krawitt, Edward L, Bizzaro, Nicola, Vergani, Diego, Bogdanos, Dimitrios P, Dalekos, George N, Milkiewicz, Piotr, Czaja, Albert J, Heathcote, E. Jenny, Hirschfield, Gideon M, Tan, Eng M, Miyachi, Kiyomitsu, Bignotto, Monica, Battezzati, Pier Maria, Lleo, Ana, Leung, Patrick S, Podda, Mauro, Gershwin, M. Eric, Invernizzi, Pietro
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.2010; Elsevier
• Subjects: Allergy and Immunology; Antigens, Nuclear - immunology; Antigens, Nuclear - metabolism; Antimitochondrial antibody; Autoantibodies; Autoantibodies - blood; Autoantigens - immunology; Autoantigens - metabolism; Biological and medical sciences; Biomarkers; Clinical Trials as Topic; enzyme-linked immunosorbent assay (ELISA); Enzyme-Linked Immunosorbent Assay - methods; Feasibility Studies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastroenterology. Liver. Pancreas. Abdomen; gp210; Humans; Immunodominant Epitopes - metabolism; Immunoglobulin A - blood; Immunoglobulin G - blood; Likelihood Functions; Liver Cirrhosis, Biliary - blood; Liver Cirrhosis, Biliary - diagnosis; Liver Cirrhosis, Biliary - immunology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Mitochondrial Proteins - immunology; Mitochondrial Proteins - metabolism; Nuclear Pore Complex Proteins - immunology; Nuclear Pore Complex Proteins - metabolism; Other diseases. Semiology; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Reproducibility of Results; Sensitivity and Specificity; sp100; BCOADC-E2; Primary biliary cirrhosis; Negative likelihood ratio; Primary sclerosing cholangitis; E2 subunit of the 2-oxo-glutarate dehydrogenase complex; PBC; OGDC-E2; enzyme-linked immunosorbent assay (ELISA); E2 subunit of the branched-chain 2-oxo-acid dehydrogenase complex; AMA; NLR; gp210; E2 subunits of the pyruvate dehydrogenase complex; PLR; AID; Enzyme-linked immunosorbent assay; Antinuclear antibodies; Receiver operator characteristic; AIH; PSC; Autoantibodies; IIF; ROC; PDC-E2; Antimitochondrial antibodies; Indirect immunofluorescence microscopy; Autoimmune hepatitis; ANA; Biomarkers; Antimitochondrial antibody; Positive likelihood ratio; sp100; Autoimmune diseases; ELISA; Autoimmunity; IgA; Immunoglobulins; Multiple; Antibody; Autoantibody; IgG; Biological marker; Hepatic disease; Isotype; Medical screening; Enzyme immunoassay; Mitochondria; Immunology; Digestive diseases; ELISA assay
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2010.09.005

Abstract A dual isotype (IgG, IgA) enzyme-linked immunosorbent assay (ELISA) designed to provide enhanced detection of primary biliary cirrhosis (PBC)-specific autoantibodies against both major mitochondrial and nuclear antigens has been developed and recently become commercially available. The assay (PBC Screen) simultaneously detects IgG and IgA autoantibodies to the immunodominant portions of the 3 major mitochondrial (MIT3) and nuclear (gp210, and sp100) antigens. The aim of this study was to compare the performance of the PBC Screen to the combined performance obtained with individual IgG ELISAs to MIT3, gp210, and sp100 on a large group of selected patients from multiple centers. A total of 1175 patients with PBC and 1232 subjects without PBC were evaluated. Non-PBC groups included healthy controls (624) as well as individuals with autoimmune hepatitis (281), primary sclerosing cholangitis (77), viral hepatitis (91 hepatitis B and 98 hepatitis C), other liver diseases (31), and other infectious or autoimmune diseases (30). The PBC Screen at the receiver operator characteristic optimized cutoff of 27.8 units, had an overall sensitivity of 83.8%, specificity of 94.7% and area under curve of 0.9212. This was similar to the specificity of 96.1% obtained by the combined results of individual MIT3, sp100, and gp210 IgG ELISAs (kappa index at 0.898). Of the 253 PBC patients without AMA detectable by immunofluorescence, 113 (44.7%) were interpreted as positive for PBC-specific autoantibodies. In conclusion, the PBC Screen is an appropriate first-line test for the diagnosis of PBC, including for patients negative for markers assessed using conventional methods.