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Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis
dc.creator | Bogdanos, D. P. | en |
dc.creator | Baum, H. | en |
dc.creator | Grasso, A. | en |
dc.creator | Okamoto, M. | en |
dc.creator | Butler, P. | en |
dc.creator | Ma, Y. | en |
dc.creator | Rigopoulou, E. | en |
dc.creator | Montalto, P. | en |
dc.creator | Davies, E. T. | en |
dc.creator | Burroughs, A. K. | en |
dc.creator | Vergani, D. | en |
dc.date.accessioned | 2015-11-23T10:23:55Z | |
dc.date.available | 2015-11-23T10:23:55Z | |
dc.date.issued | 2004 | |
dc.identifier | 10.1016/s0168-8278(03)00501-4 | |
dc.identifier.issn | 0168-8278 | |
dc.identifier.uri | http://hdl.handle.net/11615/26324 | |
dc.description.abstract | Background/Aims: Previous studies on patients with primary biliary cirrhosis (PBC) have shown extensive cross-reactivity between the dominant B- and T-cell epitopes of human pyruvate dehydrogenase complex-E2 (PDC-E2), and microbial mimics. Such observations have suggested microbial infection as having a role in the induction of anti-mitochondrial antibodies, through a mechanism of molecular mimicry. However the biological significance of these cross-reactivities is questionable, because PDC-E2 is so highly conserved among various species. Methods: Interrogating protein databases, ten non-PDC-E2 microbial sequences with high degree of similarity to PDC-E2(212-226) were found in Escherichia coli (6), Helicobacter pylori, Pseudomonas aeruginosa, Cytomegalovirus, and Haemophilus influenzae. We report on a study testing reactivity and competitive cross-reactivity against these respective peptides, and in some cases the parent protein, using sera from 55 patients with PBC, compared to reactivity of 190 pathological and 28 healthy controls. Results: Cross-reactivity to E. coli mimics was commonly seen in PBC, and in a subset of pathological controls except where there was no evidence of urinary tract infection and correlated with anti-mitochondrial reactivity. Conclusions: E. coli/PDC-E2 cross-reactive immunity characterizes primary biliary cirrhosis; the large number of E. coli immunogenic mimics may account for the dominance of the major PDC-E2 autoepitope. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. | en |
dc.source | Journal of Hepatology | en |
dc.source.uri | <Go to ISI>://WOS:000187884500006 | |
dc.subject | primary biliary cirrhosis | en |
dc.subject | microbial mimics | en |
dc.subject | Escherichia coli | en |
dc.subject | T-CELL EPITOPE | en |
dc.subject | MOLECULAR MIMICRY | en |
dc.subject | ESCHERICHIA-COLI | en |
dc.subject | DIHYDROLIPOAMIDE | en |
dc.subject | ACETYLTRANSFERASE | en |
dc.subject | NATURAL-HISTORY | en |
dc.subject | LIVER-DISEASE | en |
dc.subject | HUMAN PDC-E2 | en |
dc.subject | ANTIBODIES | en |
dc.subject | AUTOANTIBODIES | en |
dc.subject | BACTERIURIA | en |
dc.subject | Gastroenterology & Hepatology | en |
dc.title | Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis | en |
dc.type | journalArticle | en |
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