Primary Biliary Cirrhosis Dehydrogenase: Connecting Xenobiotics with the E2 Component of Pyruvate Immunoreactivity of Organic Mimeotopes of
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Xenobiotic-induced loss of tolerance in rabbits to the mitochondrial autoantigen of primary biliary cirrhosis is reversible.
Previous work has demonstrated that immunization of rabbits with the xenobiotic 6-bromohexanoate coupled to BSA breaks tolerance and induces autoantibodies to mitochondria in rabbits. Such immunized rabbits develop high-titer Abs to pyruvate dehydrogenase complex (PDC)-E2, the major autoantigen of primary biliary cirrhosis. In efforts to map the fine specificity of these autoantibodies, rabbits...
متن کاملInfection and primary biliary cirrhosis.
Primary biliary cirrhosis is an autoimmune cholestatic liver disease characterized by humoral and cellular response directed at mitochondrial autoantigens, mainly the E2 component of the pyruvate dehydrogenase complex. The etiology of PBC, like most polygenic autoimmune diseases, belongs to the "complex" category, including genetic elements and environmental factors. Many environmental factors,...
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development of autoimmune diseases were demonstrated by the example of primary biliary cirrhosis. The already known increased risk in first-degree relatives of PBC2 patients and the high concordance in monozygotic compared to dizygotic twins associated with bacteria, viruses, xenobiotics or chemical compounds (e.g., drugs like acetaminophen) have the potential to modify host proteins to render ...
متن کاملChemical xenobiotics and mitochondrial autoantigens in primary biliary cirrhosis: identification of antibodies against a common environmental, cosmetic, and food additive, 2-octynoic acid.
Emerging evidence has suggested environmental factors as causative agents in the pathogenesis of primary biliary cirrhosis (PBC). We have hypothesized that in PBC the lipoyl domain of the immunodominant E2 component of pyruvate dehydrogenase (PDC-E2) is replaced by a chemical xenobiotic mimic, which is sufficient to break self-tolerance. To address this hypothesis, based upon our quantitative s...
متن کاملT-cell autoimmunity in primary biliary cirrhosis.
1. Primary biliary cirrhosis is a chronic cholestatic liver disease with an autoimmune aetiology. The classical histopathological lesion, of portal tract biliary epithelial cell damage, is accompanied by a T-cell-rich mononuclear cell infiltrate and upregulation of cell surface markers suggestive of local T-cell activation and cytokine release. This suggests that T-cell mediated mechanisms play...
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تاریخ انتشار 2001