P-ANCAs in autoimmune liver disorders recognise human β-tubulin isotype 5 and cross-react with microbial protein FtsZ. Issue 6 (1st December 2009)

• Record Type: Journal Article
• Authors: Terjung, Birgit; Söhne, Jennifer; Lechtenberg, Berthold; Gottwein, Judith; Muennich, Marit; Herzog, Volker; Mähler, Michael; Sauerbruch, Tilman; Spengler, Ulrich
• Is Part Of: Gut. Volume 59:Issue 6(2010)
• Page Start: 808
• Page End: 816
• Publication Date: 2009-12-01
• Subjects: ANCA -- autoimmune hepatitis -- autoimmunity -- primary sclerosing cholangitis; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2008.157818
• Languages: English
• ISSNs: 0017-5749

Abstract

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.