title: Autoimmune cholangitis and primary biliary cirrhosis--an autoimmune enigma.
abstract: OBJECTIVE
  Autoimmune cholangitis/cholangiopathy (AIC) is an enigmatic disease marked by chronic cholangitis, antinuclear antibodies (ANA) and sero-negativity for conventionally detected antimitochondrial antibodies (AMA). We examined whether AIC is a distinct entity, an AMA-negative variant of primary biliary cirrhosis (PBC), or a cholangiopathic variant of autoimmune hepatitis (AIH) by comparing the clinical, laboratory and autoantibody profiles of 21 cases of AIC, 37 cases PBC and 16 cases of AIH from selected Japanese patients.
  
  
  METHODS
  The specificities of AMA and ANA were determined by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens, and the frequencies for these groups were compared.
  
  
  RESULTS
  By clinical, biochemical and histological data, AIC and PBC were similar and both were clearly distinct from AIH. Serologically, by immunofluorescence of AMA and ANA, there was polarisation. By immunoblotting, and notwithstanding the negative test for AMA, a proportion of the AIC sera reacted with the E2 subunits of the 2-oxo-acid dehydrogenase enzyme complexes, but more particularly with the lower molecular weight E2 subunits. The antinuclear reactivity in AIC was with centromere, Sp100 and nuclear pore complex proteins as in PBC, but preferentially with the nuclear pore complex.
  
  
  CONCLUSIONS
  Our results demonstrate that AIC and PBC are similar diseases. However this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC are an exception to this.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kinoshita
authors.forename: K
authors.initials: K
authors.lastname: Omagari
authors.forename: S
authors.initials: S
authors.lastname: Whittingham
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Ishibashi
authors.forename: K
authors.initials: K
authors.lastname: Sugi
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: S
authors.initials: S
authors.lastname: Kohno
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: E
authors.initials: E
authors.lastname: Penner
authors.forename: J
authors.initials: J
authors.lastname: Wesierska-Gadek
authors.forename: S
authors.initials: S
authors.lastname: Reynoso-Paz
authors.forename: M E
authors.initials: ME
authors.lastname: Gershwin
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: J A
authors.initials: JA
authors.lastname: Jois
authors.forename: I R
authors.initials: IR
authors.lastname: Mackay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D002384:Catalysis; D002761:Cholangitis / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology; D009130:Muscle, Smooth / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D009687:Nuclear Proteins; D011768:Pyruvate Dehydrogenase Complex