Document Detail

Extensive homology between the major immunodominant mitochondrial antigen in primary biliary cirrhosis and Helicobacter pylori does not lead to immunological cross-reactivity.
MedLine Citation:
PMID:  15513338     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic disease characterized by the presence of antibodies directed predominantly against the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). What provokes tolerance breakdown in PBC remains to be established, though there is evidence to indicate that microbes may induce anti-mitochondrial antibodies (AMA) through a mechanism of molecular mimicry. METHODS: Having found that urease beta (UREB)(22-36) antigen of Helicobacter pylori (HELPY) shares extensive (87%) similarity with PDC-E2(212-226), the major mitochondrial autoepitope, it was hypothesized that this would also lead to cross-reactivity. The UREB/PDC-E2 mimics were thus constructed and tested by ELISA in 112 PBC patients and 114 controls. RESULTS: Reactivity to PDC-E2(212-226) was found in 104 patients but to UREB(22-36) in only 2. In these two patients, the double reactivity was not cross-reactive. The lack of surface antibody accessibility to UREB(22-36), as demonstrated through three-dimensional model prediction analysis, may explain this unexpected finding. There was some speculation on whether HELPY UREB(22-36) might act as a cross-reactive CD4 T-cell epitope. All seven PBC patients, tested in a standard proliferation assay against PDC-E2(212-226), gave a positive response. All seven were unresponsive to HELPY UREB(22-36). The pattern of reactivity to HELPY antigens by immunoblot was similar between anti-PDC-E2-positive and negative PBC cases, as well as between PBC patients and controls. CONCLUSION: Contrary to common belief, extensive sequence homology (molecular mimicry) between self and microbe does not necessarily result in cross-reactivity. It is therefore likely that, when present, cross-reactivity between self and microbes is of biological importance.
D-P Bogdanos; H Baum; F Gunsar; D Arioli; D Polymeros; Y Ma; A K Burroughs; D Vergani
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of gastroenterology     Volume:  39     ISSN:  0036-5521     ISO Abbreviation:  Scand. J. Gastroenterol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-29     Completed Date:  2005-02-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0060105     Medline TA:  Scand J Gastroenterol     Country:  Norway    
Other Details:
Languages:  eng     Pagination:  981-7     Citation Subset:  IM    
Institute of Liver Studies, King's College Hospital, London, UK.
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MeSH Terms
Aged, 80 and over
Autoantigens / immunology
Bacterial Proteins / immunology
Cohort Studies
Cross Reactions
Dihydrolipoyllysine-Residue Acetyltransferase
Enzyme-Linked Immunosorbent Assay
Helicobacter pylori / immunology*
Immunodominant Epitopes / immunology*
Liver Cirrhosis, Biliary / blood,  immunology*
Middle Aged
Mitochondria / immunology*
Molecular Mimicry
Pyruvate Dehydrogenase Complex / analysis,  immunology*
Sampling Studies
Sensitivity and Specificity
Urease / immunology*
src Homology Domains / immunology
Reg. No./Substance:
0/Autoantigens; 0/Bacterial Proteins; 0/Immunodominant Epitopes; 0/Pyruvate Dehydrogenase Complex; EC Acetyltransferase; EC

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