title: Correlation between histopathological findings of the liver and IgA class antibodies to 2-oxo-acid dehydrogenase complex in primary biliary cirrhosis.
abstract: Although anti-mitochondrial antibody (AMA) is the characteristic serological feature of primary biliary cirrhosis (PBC), its pathogenetic role remains unclear. We tested sera from 72 Japanese patients with histologically confirmed PBC for AMA by indirect immunofluorescence, anti-pyruvate dehydrogenase complex (PDC) by enzyme inhibition assay, immunoglobulin (Ig) G class anti-PDC by ELISA, and IgG, IgM, and IgA class anti-2-oxo-acid dehydrogenase complex (2-OADC) by immunoblotting. Of the 72 sera, 60 (83%), 50 (69%), 42 (58%), and 71 (99%) were positive for AMA by immunofluorescence, enzyme inhibition assay, ELISA, and immunoblotting, respectively. There was no significant correlation between histological stages and AMA by immunofluorescence, PDC inhibitory antibodies by enzyme inhibition assay, IgG class anti-PDC antibodies by ELISA, or IgG and IgM class anti-2-OADC by immunoblotting. IgA class anti-2-OADC by immunoblotting was more frequent in stages 2-4 than in stage 1 (P = 0.0083). Of the IgA class anti-2-OADC, anti-PDC-E2 (74 kDa) and anti-E3BP (52 kDa) were more frequent in stages 2-4 than in stage 1 (P = 0.0253 and 0.0042, respectively). Further examination of histopathological findings in 53 of 72 liver biopsy specimens showed that IgA class anti-PDC-E2 and IgA class anti-E3BP were associated with bile duct loss, and IgA class anti-PDC-E2 was also associated with interface hepatitis and atypical ductular proliferation. IgA is known to be secreted into the bile through biliary epithelial cells, implying that IgA class anti-PDC-E2 and E3BP may have a specific pathogenetic role during their transport into the bile by binding to their target antigen(s) in biliary epithelial cells, and this may be followed by dysfunction and finally destruction of biliary epithelial cells. Our present results suggest that these autoantibodies against 2-OADC detected by immunoblotting may be associated with the pathogenesis and pathologic progression of PBC.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Masuda
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Omagari
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohba
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hazama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kadokawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Kenji
authors.initials: K
authors.lastname: Hayashida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hayashida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007075:Immunoglobulin M / Q000032:analysis*; D007150:Immunohistochemistry; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011768:Pyruvate Dehydrogenase Complex / Q000032:analysis*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D011768:Pyruvate Dehydrogenase Complex; D051047:Dihydrolipoyllysine-Residue Acetyltransferase