title: Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.|Institute for Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Sebastian Torben
authors.initials: ST
authors.lastname: Jendrek
authors.affiliation: Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gotthardt
authors.affiliation: Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nitzsche
authors.affiliation: Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Laila
authors.initials: L
authors.lastname: Widmann
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Korf
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
authors.forename: Maike Anna
authors.initials: MA
authors.lastname: Michaels
authors.affiliation: Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Weiss
authors.affiliation: Centre for Liver Research and NIHR Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
authors.forename: Evaggelia
authors.initials: E
authors.lastname: Liaskou
authors.affiliation: Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Mette
authors.initials: M
authors.lastname: Vesterhus
authors.affiliation: Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine and Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine and K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Tom Hemming
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Mindorf
authors.affiliation: Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Bär
authors.affiliation: Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Teegen
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.|Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Schröder
authors.affiliation: Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Ehlers
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Christoph Matthias
authors.initials: CM
authors.lastname: Hammers
authors.affiliation: Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Komorowski
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Fellermann
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Derer
authors.affiliation: Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine and Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, Institute of Clinical Medicine and K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Johannes Roksund
authors.initials: JR
authors.lastname: Hov
authors.affiliation: Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001650:Bile Duct Neoplasms / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D018281:Cholangiocarcinoma / Q000097:blood*; D015209:Cholangitis, Sclerosing / Q000097:blood*; D003093:Colitis, Ulcerative / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000097:blood; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D007070:Immunoglobulin A
keywords: AUTO-ANTIBODIES; CHOLANGIOCARCINOMA; INFLAMMATORY BOWEL DISEASE; PANCREATIC ANTIBODIES; PRIMARY SCLEROSING CHOLANGITIS