Summary
Autoantibodies to the recently described mitochondrial autoantigen, pyruvate dehydrogenase, have been shown to be specific for primary biliary cirrhosis. In the present study we describe enzyme-linked immunosorbent assays to detect antibodies of IgG, IgA, and IgM classes reactive with pyruvate dehydrogenase. These assays showed high sensitivity (95%) and specificity (100%) for primary biliary cirrhosis when evaluated in 28 patients with primary biliary cirrhosis, 59 disease controls, and 214 healthy persons. Quantitation of these autoantibodies by calculating the areas under the sera titration curves of 10 primary biliary cirrhosis patients indicated that an increase in IgA antibodies to pyruvate dehydrogenase is related to more rapid disease progression.
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Berg PA, Klein R, Lindenborn-Fotinos J, Klöppel W, ATPase associated antigen (M2): marker antigen for serological diagnosis of primary biliary cirrhosis. Lancet II:1423, 1982
Berg PA, Klein R, Molecular determination of the primary biliary cirrhosis-specific M2 antigen. Hepatology 8:200, 1988
Brown RA, Swanson Beck J, Statistics on microcomputers: a non-algebraic guide to the appropriate use of statistical packages in biomedical research and pathology laboratory practice. J Clin Pathol 42:225, 1989
Doniach D, Roitt CM, Walker JG, Sherlock S, Tissue antibodies in primary biliary cirrhosis, active chronic (lupoid) hepatitis, cryptogenic cirrhosis and other liver disease and their clinical implication. Clin Exp Immunol 60:77, 1966
François-Gérard P, Rentier B, Elucidation of non-parallel EIA curves. J Immunol Methods 111:59, 1988
Fregeau DR, Davis PA, Danner DJ, Ansari A, Coppel RL, Dickson ER, Gershwin ME, Mitochondrial antibodies of primary cirrhosis recognize dihydrolipoamide acyl-transferase and inhibit enzyme function of the branched chain α-ketoacid dehydrogenase complex. J Immunol 142:3815, 1989
Gershwin ME, Mackay IR, Sturgess A, Coppel RL, Identification and specificity a cDNA encoding the 70 kD mitochondrial antigen recognized in primary biliary cirrhosis. J Immunol 138:3525, 1987
Gershwin ME, Coppel RL, Mackay IR, Primary biliary cirrhosis and mitochondrial autoantigens—insights from molecular biology. Hepatology 8:147, 1988
Heseltine L, Turner IB, Fussey SPM, Kelly PJ, James OFW, Yeaman SJ, Bassendine MF, Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzyme and correlation with disease progression. Gastroenterology 99: 1786, 1990
Ishü H, Saifuku K, Namihisa T, Reactivities and clinical relevance of antimitochondrial antibodies to four mitochondrial inner membrane proteins in sera of patients with primary biliary cirrhosis. Hepatology 7:134, 1987
Iwayama T, Leung PSC, Rowley M, Munoz S, Nishioka M, Nakagawa T, Dickson ER, Coppel RL, Mackay IR, Gershwin ME, Comparative immunoreactive profiles of Japanese and American patients with primary biliary cirrhosis against mitochondrial autoantigens. Int Arch Allergy Immunol 99:28, 1992
Joplin R, Lindsay JG, Johnson GD, Strain A, Neuberger J, Membrane dihydrolipoamide acetyltransferase (E2) on human biliary epithelial cells in primary biliary cirrhosis. Lancet 339:93, 1992
Krams SM, Van de Water J, Coppel RL, Esquivel C, Roberts J, Ansari A, Gershwin ME, Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis. Hepatology 12:306, 1990
Lehtonen O-P, Eerola E, The effect of different antibody affinities on ELISA absorbance and titer. J Immunol Methods 54:233, 1982
Mutimer DJ, Fussey SPM, Yeaman SJ, Kelly PJ, James OFW, Bassendine MF, Frequency of IgG and IgM autoantibodies to four specific M2 mitochondrial autoantigens in primary biliary cirrhosis. Hepatology 10:403, 1989
Sheuer PJ, Primary biliary cirrhosis: diagnosis, pathology and pathogenesis. Postgruad Med J 59 [Suppl 4]:106, 1983
Surh CD, Cooper AE, Coppel RL, Leung P, Ahmed A, Dickson R, Gershwin ME, The predominance of IgG3 and IgM isotype fused mitochondrial polypeptide in patients with primary biliary cirrhosis. Hepatology 8:290, 1988
Surh CD, Roche TE, Danner DJ, Ansari A, Coppel RL, Prindiville T, Dickson ER, Gershwin ME, Antimitochondrial antibodies in primary biliary cirrhosis recognize crossreactive epitopes on protein X and dihydro-lipoamide acetyltransferase of pyruvate dehydrogenase complex. Hepatology 10:127, 1989
Tijssen P, Practice and theory of enzyme immuno-assays. In: Burdon RH, Van Knippenberg PH (eds) Laboratory techniques in biochemistry and molecular biology. Elsevier, Amsterdam, pp 385–422, 1985
Tsuruya T, Detection of anti-pyruvate dehydrogenase complex antibody in primary biliary cirrhosis by an enzyme-linked immunosorbent assay. Gastroenterol Jpn 25:471, 1990
Uibo R, Mackay IR, Rowley M, Humphiries P, Armstrong MCD, McNeilage J, Inhibition of enzyme function by human autoantibodies to an autoantigen pyruvate dehydrogenase E2: different epitope for spontaneous human and induced rabbit autoantibodies. Clin Exp Immunol 80:19, 1990
Van de Water J, Cooper A, Surh CD, Coppel R, Danner D, Ansari A, Dickson R, Gershwin ME, Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. N Engl J Med 320:1377, 1989
Walker JG, Doniach D, Roitt IM, Sherlock S, Serological tests in diagnosis of primary biliary cirrhosis. Lancet I:827, 1965
Yeaman SJ, Fussey SPM, Danner DJ, James OFW, Mutimer DJ, Bassendine MF, Primary biliary cirrhosis: identification of two major M2 mitochondrial autoantigens. Lancet I:1067, 1988
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Kisand, K., Kisand, K., Salupere, V. et al. Enzyme-linked immunosorbent assays for the determination of IgG, IgA, and IgM autoantibodies to pyruvate dehydrogenase in primary biliary cirrhosis. Int J Clin Lab Res 24, 98–101 (1994). https://doi.org/10.1007/BF02593908
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DOI: https://doi.org/10.1007/BF02593908