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Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis
  1. Sebastian Torben Jendrek1,2,
  2. Daniel Gotthardt3,
  3. Thomas Nitzsche4,
  4. Laila Widmann3,
  5. Tobias Korf1,
  6. Maike Anna Michaels1,
  7. Karl-Heinz Weiss3,
  8. Evaggelia Liaskou5,
  9. Mette Vesterhus6,7,
  10. Tom Hemming Karlsen6,8,9,
  11. Swantje Mindorf4,
  12. Peter Schemmer10,
  13. Florian Bär1,
  14. Bianca Teegen4,
  15. Torsten Schröder1,11,
  16. Marc Ehlers11,
  17. Christoph Matthias Hammers12,
  18. Lars Komorowski4,
  19. Hendrik Lehnert1,
  20. Klaus Fellermann1,
  21. Stefanie Derer1,
  22. Johannes Roksund Hov6,8,9,
  23. Christian Sina1
  1. 1Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
  2. 2Institute for Anatomy, University of Lübeck, Lübeck, Germany
  3. 3Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany
  4. 4Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany
  5. 5Centre for Liver Research and NIHR Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
  6. 6Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway
  7. 7National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
  8. 8Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine and Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway
  9. 9Faculty of Medicine, Institute of Clinical Medicine and K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway
  10. 10Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
  11. 11Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany
  12. 12Department of Dermatology, University of Lübeck, Lübeck, Germany
  1. Correspondence to Professor Christian Sina, Medical Department 1, University of Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany; christian.sina{at}uk-sh.de

Abstract

Objective Pancreatic autoantibodies (PABs), comprising antibodies against glycoprotein 2 (anti-GP2), are typically associated with complicated phenotypes in Crohn's disease, but have also been observed with variable frequencies in patients with UC. In a previous study, we observed a high frequency of primary sclerosing cholangitis (PSC) in patients with anti-GP2-positive UC. We therefore aimed to characterise the role of anti-GP2 in PSC.

Design In an evaluation phase, sera from 138 well-characterised Norwegian patients with PSC were compared with healthy controls (n=52), and patients with UC without PSC (n=62) for the presence of PABs by indirect immunofluorescence. Further, 180 German patients with PSC served as a validation cohort together with 56 cases of cholangiocarcinoma without PSC, 20 of secondary sclerosing cholangitis (SSC) and 18 of autoimmune hepatitis.

Results Anti-GP2 IgA specifically occurred at considerable rates in large bile duct diseases (cholangiocarcinoma=36%, PSC and SSC about 50%). In PSC, anti-GP2 IgA consistently identified patients with poor survival during follow-up (Norwegian/German cohort: p Log Rank=0.016/0.018). Anti-GP2 IgA was associated with the development of cholangiocarcinoma in both PSC cohorts, yielding an overall OR of cholangiocarcinoma in patients with anti-GP2 IgA-positive PSC of 5.0 (p=0.001). Importantly, this association remained independent of disease duration, bilirubin level and age.

Conclusions Anti-GP2 IgA can be hypothesised as a novel marker in large bile duct diseases. In particular, in PSC, anti-GP2 IgA identified a subgroup of patients with severe phenotype and poor survival due to cholangiocarcinoma. Anti-GP2 IgA may therefore be a clinically valuable tool for risk stratification in PSC.

  • PRIMARY SCLEROSING CHOLANGITIS
  • PANCREATIC ANTIBODIES
  • CHOLANGIOCARCINOMA
  • AUTO-ANTIBODIES
  • INFLAMMATORY BOWEL DISEASE

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