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Gut. 2017 Jan;66(1):137-144. doi: 10.1136/gutjnl-2016-311739. Epub 2016 Jul 12.

Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis.

Author information

1
Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.
2
Institute for Anatomy, University of Lübeck, Lübeck, Germany.
3
Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany.
4
Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany.
5
Centre for Liver Research and NIHR Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
6
Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.
7
National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.
8
Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine and Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
9
Faculty of Medicine, Institute of Clinical Medicine and K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
10
Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.
11
Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
12
Department of Dermatology, University of Lübeck, Lübeck, Germany.

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.

KEYWORDS:

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

PMID:
27406039
DOI:
10.1136/gutjnl-2016-311739
[Indexed for MEDLINE]

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