title: Antibodies to pyruvate dehydrogenase in primary biliary cirrhosis: correlation with histology.
abstract: Antimitochondrial antibodies to pyruvate dehydrogenase are the hallmark of primary biliary cirrhosis. Their pathogenic role has not been proven, although antibodies to pyruvate dehydrogenase are bound to biliary epithelium. The aim of this study was to characterize serum IgA antibodies to pyruvate dehydrogenase and to evaluate their response to different treatment regimens. We also compared the level of antibodies with severity of histological lesions and the data of biochemical liver tests. Serum samples were collected at baseline and after 24 months from 61 primary biliary cirrhosis patients, whereas 23 patients were treated with ursodeoxycholic acid, 20 with colchicine, and 18 with placebo. ELISA was used to detect antibodies to pyruvate dehydrogenase. IgA and IgG were separated with jacalin and protein-A, respectively. Capacity of immunoglobulins to inhibit enzymatic activity was detected by spectrophotometric observation of the rate of enzyme reaction. 49 (80.3%) of the 61 patients possessed IgA antibodies to pyruvate dehydrogenase. Significant decrease in IgA antibodies was observed only in the ursodeoxycholic acid group (p<0.05). 15 of 18 IgA preparations and all 24 IgG preparations of patients' sera were inhibitory towards pyruvate dehydrogenase (mean inhibitory percent +/-SD: 42+/-33.4% and 79+/-22.4%, respectively, at a protein concentration of 100 microg/ml). The level of serum antibodies to pyruvate dehydrogenase correlated with several histological parameters (fibrosis, inflammatory infiltrate), but not with biochemical parameters. Our data reveal that IgA antibodies to pyruvate dehydrogenase inhibit enzyme function. The correlation between antibodies to pyruvate dehydrogenase and histological parameters might suggest the pathogenic role of these antibodies.
authors.affiliation: Institute of General and Molecular Pathology, Department of Immunology, University of Tartu, Estonia.
authors.forename: K E
authors.initials: KE
authors.lastname: Kisand
authors.forename: K V
authors.initials: KV
authors.lastname: Kisand
authors.forename: A L
authors.initials: AL
authors.lastname: Karvonen
authors.forename: M
authors.initials: M
authors.lastname: Vuoristo
authors.forename: J
authors.initials: J
authors.lastname: Mattila
authors.forename: J
authors.initials: J
authors.lastname: Mäkinen
authors.forename: R
authors.initials: R
authors.lastname: Uibo
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000032:analysis; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001663:Bilirubin / Q000097:blood; D003078:Colchicine / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000418:Albumins; D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011768:Pyruvate Dehydrogenase Complex; D014580:Ursodeoxycholic Acid; D001663:Bilirubin; D003078:Colchicine