RT Journal Article
SR Electronic
T1 Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 137
OP 144
DO 10.1136/gutjnl-2016-311739
VO 66
IS 1
A1 Sebastian Torben Jendrek
A1 Daniel Gotthardt
A1 Thomas Nitzsche
A1 Laila Widmann
A1 Tobias Korf
A1 Maike Anna Michaels
A1 Karl-Heinz Weiss
A1 Evaggelia Liaskou
A1 Mette Vesterhus
A1 Tom Hemming Karlsen
A1 Swantje Mindorf
A1 Peter Schemmer
A1 Florian Bär
A1 Bianca Teegen
A1 Torsten Schröder
A1 Marc Ehlers
A1 Christoph Matthias Hammers
A1 Lars Komorowski
A1 Hendrik Lehnert
A1 Klaus Fellermann
A1 Stefanie Derer
A1 Johannes Roksund Hov
A1 Christian Sina
YR 2017
UL http://gut.bmj.com/content/66/1/137.abstract
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.