Anti-pyruvate dehydrogenase autoantibodies in primary biliary cirrhosis |
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Authors: | N. Zurgil R. Bakimer M. Kaplan P. Youinou Y. Shoenfeld |
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Affiliation: | (1) Research Unit of Autoimmune Diseases, Department of Medicine B, , Sheba Medical Center, 52621 Tel-Hashome, Israel;(2) BioHytech (Israel) Ltd, Ramat-Gan, Israel;(3) Department of Medicine, Gastroenterology Division, Tufts University School of Medicine and New England Medical Center Hospital, Boston, Massachusetts;(4) Laboratoire D'Immunologic Centre, Hospitalier Regional et Universitaire de Brest, Brest, France |
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Abstract: | Antimitochondrial antibodies (AMA) may be detected in 95% of patients with primary biliary cirrhosis (PBC). The target autoantigens for the AMA were recently identified as four closely related metabolic enzymes located in the mitochondria. We have purified the pyruvate dehydrogenase (PDH) enzyme from bovine heart, showing that all PBC sera reacted with a 74-kd band. PDH was utilized to establish an ELISA assay for detecting the relevant antibodies. One hundred twelve of 120 sera from patients with PBC (95%) reacted with the PDH but none of the 201 control sera, including normal subjects and a panel of sera from other patients with liver diseases, showed similar reactivity. In 77% of the PBC sera the anti-PDH antibody isotype was identified as a combination of IgG and IgM, while in 18% only IgM was detected. In 5% of the sera the isotype was confined to IgG. PBC sera specifically inhibited the PDH enzyme activity. The enzyme inhibition correlated with the anti-PDH antibody titers. Thus, PDH seems to be one of the major target epitopes for AMA observed in sera of patients with PBC. |
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Keywords: | Antimitochondrial antibodies pyruvate dehydrogenase primary biliary cirrhosis autoimmunity autoantibodies |
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