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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
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  •   University of Thessaly Institutional Repository
  • Επιστημονικές Δημοσιεύσεις Μελών ΠΘ (ΕΔΠΘ)
  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ.
  • View Item
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Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its lactobacillus mimic

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Author
Bogdanos, D. P.; Baum, H.; Okamoto, M.; Montalto, P.; Sharma, U. C.; Rigopoulou, E. I.; Vlachogiannakos, J.; Ma, Y.; Burroughs, A. K.; Vergani, D.
Date
2005
DOI
10.1002/hep.20788
Keyword
bacterial protein
beta galactosidase
epitope
immunoglobulin antibody
immunoglobulin G3
immunoglobulin G3 antibody
immunoglobulin G4
mitochondrion antibody
pyruvate dehydrogenase complex
pyruvate dehydrogenase complex E2
unclassified drug
adult
antibody detection
antigen binding
article
binding affinity
controlled study
cross reaction
enzyme activity
enzyme linked immunosorbent assay
Escherichia coli
female
human
Lactobacillus delbrueckii
major clinical study
male
primary biliary cirrhosis
priority journal
protein motif
sequence homology
serology
Aged
Amino Acid Sequence
Autoimmunity
beta-Galactosidase
Cross Reactions
Dihydrolipoyllysine-Residue Acetyltransferase
Epitopes
Humans
Immunoglobulin G
Lactobacillus
Liver Cirrhosis, Biliary
Middle Aged
Mitochondria
Molecular Sequence Data
Metadata display
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.
URI
http://hdl.handle.net/11615/26325
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  • Δημοσιεύσεις σε περιοδικά, συνέδρια, κεφάλαια βιβλίων κλπ. [9714]

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