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p-ANCAs in autoimmune liver disorders recognise human β-tubulin isotype 5 and cross-react with microbial protein FtsZ
  1. Birgit Terjung1,
  2. Jennifer Söhne1,
  3. Berthold Lechtenberg1,
  4. Judith Gottwein1,
  5. Marit Muennich1,
  6. Volker Herzog2,
  7. Michael Mähler3,
  8. Tilman Sauerbruch1,
  9. Ulrich Spengler1
  1. 1Department of Internal Medicine, University of Bonn, Bonn, Germany
  2. 2Institute of Cell Biology, University of Bonn, Bonn, Germany
  3. 3Biomedical Diagnostics, Hannover, Germany
  1. Correspondence to Dr Birgit Terjung, Department of Internal Medicine, University of Bonn, Sigmund-Freud-Strasse 25, Bonn D-53105, Germany; birgit.terjung{at}ukb.uni-bonn.de

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.

Methods and Results Here, it is reported that p-ANCAs in autoimmune liver disorders react with β-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.

  • ANCA
  • autoimmune hepatitis
  • autoimmunity
  • primary sclerosing cholangitis

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Footnotes

  • Linked articles 203091.

  • Funding Lise-Meitner-Foundation, Germany, and Bonfor Foundation, University of Bonn, Germany.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the University of Bonn ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patent application An international patent application (PCT/EP05/54104) was filed.

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