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J Hepatol. 2004 Jan;40(1):31-9.

Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis.

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  • 1Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5 9RS, UK.

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.

PMID:
14672611
[PubMed - indexed for MEDLINE]
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