Mitochondrial Antigens

BAUM, HAROLD

doi:10.1016/b978-0-12-152517-0.50010-4

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“…The loss of B-cell tolerance toward mitochondrial antigens is a highly specific serological marker of primary biliary cirrhosis (PBC) present at high titers in patients with PBC (Baum, 1994;Berg and Klein, 1995). PBC is a chronic cholestatic liver disease predominantly affecting middleaged women.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a Lipoyl Domain‐Independent B‐Cell Autoepitope on the Human Branched‐Chain Acyltransferase in Primary Biliary Cirrhosis and Overlap Syndrome with Autoimmune Hepatitis

Csepregi

Obermayer-Straub

Kneip

et al. 2003

Journal of Immunology Research

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Background and aims: Antimitochondrial antibodies (AMA) which recognize pyruvate acetyltransferase (PDC-E2) represent a highly diagnostic feature of primary biliary cirrhosis (PBC). The analysis of immunofluorescence (IF)-AMA-positive sera in PBC patients indicates a conformational epitope located within the lipoyl binding domain of bovine branched-chain acyltransferase (BCKADC-E2) alone or in combination with AMA directed against PDC-E2 the significance of which is presently unclear. In the present study, immunoreactivities and disease associations of AMA against BCKADC-E2 were analyzed. B-cell autoepitopes on BCKADC-E2 were mapped by immunoprecipitation assay. Methods: Sera of 96 IF-AMA-positive patients with serological evidence of anti-BCKADC-E2 alone (n=26), anti-PDC-E2 alone (n=15), and both anti-BCKADC-E2 and anti-PDC-E2 (n=55) were analyzed by Western blot and ELISA in addition to an analysis of B cell autoepitopes on BCKADC-E2 by immunoprecipitation using in vitro translated, unmodified human proteins. Ninety-four patients without IF-AMA [blood donors (n=30), rheumatoid arthritis (n=40), autoimmune hepatitis (AIH) (n=10) and primary sclerosing cholangitis (PSC) (n=14] served as controls. Results: Eighty of 81 (99%) sera positive for BCKADC-E2 recognized the full length, mature protein, while only 2/10 AIH sera and none of the other controls showed reactivity. Of the 68 PBC sera 58 (85%) recognized the N-terminus consisting of aa 1-144 representing the lipoyl domain. Surprisingly, C-terminal sequences (aa 143-421) were recognized by 46 out of 68 sera (68%). Three PBC sera reacted with the C-terminus only. Only 1/7 serum from patients with an “overlap syndrome of PBC and AIH” was reactive with C-terminal sequences. Conclusions: Our analysis of BCKADC-E2-positive PBC sera identified a novel B cell epitope on the C-terminal part of the human protein. Our data indicate that a distinct subset of AMA recognize sequence(s) on BCKADC-E2 which located outside of the lipoyl binding domain. The absence of immunoreactivity against C-terminal sequences may serve as a marker differentiating patients with PBC and overlap syndrome of PBC with AIH.

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Section: Introductionmentioning

confidence: 99%