Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its lactobacillus mimic
dc.creator | Bogdanos, D. P. | en |
dc.creator | Baum, H. | en |
dc.creator | Okamoto, M. | en |
dc.creator | Montalto, P. | en |
dc.creator | Sharma, U. C. | en |
dc.creator | Rigopoulou, E. I. | en |
dc.creator | Vlachogiannakos, J. | en |
dc.creator | Ma, Y. | en |
dc.creator | Burroughs, A. K. | en |
dc.creator | Vergani, D. | en |
dc.date.accessioned | 2015-11-23T10:23:56Z | |
dc.date.available | 2015-11-23T10:23:56Z | |
dc.date.issued | 2005 | |
dc.identifier | 10.1002/hep.20788 | |
dc.identifier.issn | 2709139 | |
dc.identifier.uri | http://hdl.handle.net/11615/26325 | |
dc.description.abstract | The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2212-226 and hsp's is a cross-reactive target. Having found that this same motif is present only in β-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from 100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia colt (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL266-280 LACDE antibodies were restricted to AMA-positive patients (54 of 95, 57%) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12%; P < .001) had anti-BGAL266-280 antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL266-280/PDC-E2212-226 reactivity of the IgG3 isotype was found in 52 (52%) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL266-280/PDCXE2212-226 reactivity was due to cross-reactivity as confirmed via competition ELISA. Antibody affinity for BGAL266-280 was greater than for PDC-E2 mimics. Preincubation of a multireactive serum with BGAL266-280 reduced the inhibition of enzymatic activity by 40%, while marginal effect (12%) or no effect (2%) was observed in human or ECOLIPDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC. Copyright © 2005 by the American Association for the Study of Liver Diseases. | en |
dc.source | Hepatology | en |
dc.source.uri | http://www.scopus.com/inward/record.url?eid=2-s2.0-23044467085&partnerID=40&md5=4bdd6130d733654a155df721ad6f5742 | |
dc.subject | bacterial protein | en |
dc.subject | beta galactosidase | en |
dc.subject | epitope | en |
dc.subject | immunoglobulin antibody | en |
dc.subject | immunoglobulin G3 | en |
dc.subject | immunoglobulin G3 antibody | en |
dc.subject | immunoglobulin G4 | en |
dc.subject | mitochondrion antibody | en |
dc.subject | pyruvate dehydrogenase complex | en |
dc.subject | pyruvate dehydrogenase complex E2 | en |
dc.subject | unclassified drug | en |
dc.subject | adult | en |
dc.subject | antibody detection | en |
dc.subject | antigen binding | en |
dc.subject | article | en |
dc.subject | binding affinity | en |
dc.subject | controlled study | en |
dc.subject | cross reaction | en |
dc.subject | enzyme activity | en |
dc.subject | enzyme linked immunosorbent assay | en |
dc.subject | Escherichia coli | en |
dc.subject | female | en |
dc.subject | human | en |
dc.subject | Lactobacillus delbrueckii | en |
dc.subject | major clinical study | en |
dc.subject | male | en |
dc.subject | primary biliary cirrhosis | en |
dc.subject | priority journal | en |
dc.subject | protein motif | en |
dc.subject | sequence homology | en |
dc.subject | serology | en |
dc.subject | Aged | en |
dc.subject | Amino Acid Sequence | en |
dc.subject | Autoimmunity | en |
dc.subject | beta-Galactosidase | en |
dc.subject | Cross Reactions | en |
dc.subject | Dihydrolipoyllysine-Residue Acetyltransferase | en |
dc.subject | Epitopes | en |
dc.subject | Humans | en |
dc.subject | Immunoglobulin G | en |
dc.subject | Lactobacillus | en |
dc.subject | Liver Cirrhosis, Biliary | en |
dc.subject | Middle Aged | en |
dc.subject | Mitochondria | en |
dc.subject | Molecular Sequence Data | en |
dc.title | Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its lactobacillus mimic | en |
dc.type | journalArticle | en |
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