title: p-ANCAs in autoimmune liver disorders recognise human beta-tubulin isotype 5 and cross-react with microbial protein FtsZ.
abstract: OBJECTIVE
  Autoimmune hepatitis and primary sclerosing cholangitis are chronic inflammatory disorders of unknown aetiology, frequently associated with the presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) directed against an unknown antigen of myeloid cells.
  
  
  RESULTS
  Here, it is reported that p-ANCAs in autoimmune liver disorders react with beta-tubulin isotype 5 (TBB-5) as autoantigen as well as with its evolutionary bacterial precursor protein FtsZ. Both proteins were confirmed as antigens of p-ANCAs in autoimmune liver disorders by demonstrating reactivity of ANCA-positive sera with recombinant TBB-5 (72-88%) and FtsZ (64-82%) on immunoblots and antigen-specific abrogation of ANCA immunofluorescence when sera had been preabsorbed with tubulin and FtsZ. Using sera from interleukin 10-deficient mice (Il10(-)/(-)), an animal model of inflammatory bowel disease, it was also demonstrated that antibodies against TBB-5 are generated in response to intestinal microorganisms. However, unlike autoimmune liver disorders, human antibodies to FtsZ in the absence of TBB-5 antibodies were also a frequent finding in non-autoimmune liver diseases (up to 95%). Reactivity to TBB-5 without the presence of FtsZ antibodies was found in very few cases (<1%) in autoimmune liver disorders.
  
  
  CONCLUSIONS
  Thus, p-ANCAs in autoimmune liver diseases are directed against human TBB-5 cross-reacting with the bacterial protein FtsZ, probably reflecting an abnormal immune response to intestinal microorganisms in susceptible, possibly genetically predisposed individuals.
authors: Department of Internal Medicine, University of Bonn, Sigmund-Freud-Strasse 25, Bonn D-53105, Germany. birgit.terjung@ukb.uni-bonn.de
authors: Birgit
authors: B
authors: Terjung
authors: Jennifer
authors: J
authors: Söhne
authors: Berthold
authors: B
authors: Lechtenberg
authors: Judith
authors: J
authors: Gottwein
authors: Marit
authors: M
authors: Muennich
authors: Volker
authors: V
authors: Herzog
authors: Michael
authors: M
authors: Mähler
authors: Tilman
authors: T
authors: Sauerbruch
authors: Ulrich
authors: U
authors: Spengler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001324:Autoantigens / Q000032:analysis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D015209:Cholangitis, Sclerosing / Q000276:immunology*; D003429:Cross Reactions; D003598:Cytoskeletal Proteins / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010449:Peptide Mapping / Q000379:methods; D011994:Recombinant Proteins / Q000276:immunology; D014404:Tubulin / Q000276:immunology*; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D011994:Recombinant Proteins; D014404:Tubulin