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Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic
Author(s) -
Bogdanos DimitriosPetrou,
Baum Harold,
Okamoto Manabu,
Montalto Paolo,
Sharma Umesh C.,
Rigopoulou Eirini I.,
Vlachogiannakos John,
Ma Yun,
Burroughs Andrew K.,
Vergani Diego
Publication year - 2005
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20788
Subject(s) - antibody , primary biliary cirrhosis , serology , autoantibody , isotype , cross reactivity , subclass , biology , immunology , microbiology and biotechnology , cross reactions , monoclonal antibody
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‐E2 212‐226 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 coli (ECOLI) PDC‐E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti‐BGAL 266‐280 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‐BGAL 266‐280 antibodies, mainly of the IgG4 subclass. ECOLI PDC‐E2 reactivity was virtually absent. BGAL 266‐280 /PDC‐E2 212‐226 reactivity of the IgG3 isotype was found in 52 (52%) AMA‐positive PBC patients but in only 1 of the controls ( P < .001). LACDE BGAL 266‐280 /PDC‐E2 212‐226 reactivity was due to cross‐reactivity as confirmed via competition ELISA. Antibody affinity for BGAL 266‐280 was greater than for PDC‐E2 mimics. Preincubation of a multireactive serum with BGAL 266‐280 reduced the inhibition of enzymatic activity by 40%, while marginal effect (12%) or no effect (2%) was observed in human or ECOLI PDC‐E2 mimics. In conclusion , IgG3 antibodies to BGAL LACDE cross‐react with the major mitochondrial autoepitope and are characteristic of PBC. (H EPATOLOGY 2005;42:458–465.)