title: Analysis of the clinical relevance of antimitochondrial antibodies to the β- and γ-subunits of the F1F0-ATPase in patients with primary biliary cirrhosis.
abstract: BACKGROUND
  In a recent study we showed that in patients with primary biliary cirrhosis (PBC) being positive or negative for anti-M2 antibodies reacting with the 2-oxoacid-dehydrogenase complex (ODC) also antibodies to the beta- and gamma-subunits of F1F0-ATPase (anti-β, anti-γ) occur. This is a mitochondrial enzyme but parts are also expressed on plasma membranes of endothelial cells. Here we wanted to analyse in more detail their clinical relevance.
  
  
  METHODS
  Fifty-nine untreated and histologically defined PBC patients who had been followed for at least five years were included into the study (51 anti-M2 positive, 8 anti-M2 negative). Twenty-three of them were treated in the follow up with ursodeoxycholic acid (UDCA), eight received during a trial methotrexate (MTX). In 13 patients orthotopic liver transplantation (OLT) had to be performed. Serum samples before and during therapy were available. Patients were analysed with respect to laboratory parameters, disease activity and histological stages.Patients' sera were tested by ELISA for IgG- and IgM-antibodies against the beta- and gamma-subunits which had been recombinant expressed in E.coli and highly purified by electro-elution from SDS-gels after electrophoresis.
  
  
  RESULTS
  Fifty-nine percent of the anti-M2 positive and 50% of the anti-M2 negative PBC patients had anti-β- and/or anti-γ-antibodies. There were no differences between anti-β- and/or anti-γ-antibody positive or negative patients with respect to biochemical parameters, immunoglobulins, histological stages or disease activity. Antibody reactivity significantly decreased during UDCA and MTX-treatment and also after OLT.
  
  
  CONCLUSIONS
  Antibodies to the β- and γ-subunits of F1F0-ATPase occur in anti-M2 positive and -negative PBC but do not have any relevance with respect to clinical activity or prognosis. However, in contrast to the anti-M2 antibodies they decrease during UDCA and immunosuppressive therapy.
authors.affiliation: Department of Internal Medicine II, University of Tuebingen, Tuebingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Nann
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Berg
authors.forename: Beate E
authors.initials: BE
authors.lastname: Preuss
authors.forename: Reinhild
authors.initials: R
authors.lastname: Klein
mesh_terms: D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000276:immunology*; D006180:Proton-Translocating ATPases / Q000276:immunology*; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D006180:Proton-Translocating ATPases; D008727:Methotrexate