PT  - JOURNAL ARTICLE
AU  - Sebastian Torben Jendrek
AU  - Daniel Gotthardt
AU  - Thomas Nitzsche
AU  - Laila Widmann
AU  - Tobias Korf
AU  - Maike Anna Michaels
AU  - Karl-Heinz Weiss
AU  - Evaggelia Liaskou
AU  - Mette Vesterhus
AU  - Tom Hemming Karlsen
AU  - Swantje Mindorf
AU  - Peter Schemmer
AU  - Florian Bär
AU  - Bianca Teegen
AU  - Torsten Schröder
AU  - Marc Ehlers
AU  - Christoph Matthias Hammers
AU  - Lars Komorowski
AU  - Hendrik Lehnert
AU  - Klaus Fellermann
AU  - Stefanie Derer
AU  - Johannes Roksund Hov
AU  - Christian Sina
TI  - Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis
AID  - 10.1136/gutjnl-2016-311739
DP  - 2017 Jan 01
TA  - Gut
PG  - 137--144
VI  - 66
IP  - 1
4099  - http://gut.bmj.com/content/66/1/137.short
4100  - http://gut.bmj.com/content/66/1/137.full
SO  - Gut2017 Jan 01; 66
AB  - 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.