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

• Verfasst von: Jendrek, Sebastian Torben [VerfasserIn]
• Verfasst von: Gotthardt, Daniel [VerfasserIn]
• Verfasst von: Widmann, Laila Virginia [VerfasserIn]
• Verfasst von: Weiss, Karl Heinz [VerfasserIn]
• Verfasst von: Schemmer, Peter [VerfasserIn]
• Titel: Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis
• Verf.angabe: Sebastian Torben Jendrek, Daniel Gotthardt, Thomas Nitzsche, Laila Widmann, Tobias Korf, Maike Anna Michaels, Karl-Heinz Weiss, Evaggelia Liaskou, Mette Vesterhus, Tom Hemming Karlsen, Swantje Mindorf, Peter Schemmer, Florian Bär, Bianca Teegen, Torsten Schröder, Marc Ehlers, Christoph Matthias Hammers, Lars Komorowski, Hendrik Lehnert, Klaus Fellermann, Stefanie Derer, Johannes Roksund Hov, Christian Sina
• Jahr: 2017
• Jahr des Originals: 2016
• Umfang: 8 S.
• Fussnoten: First published July 12, 2016 ; Gesehen am 21.08.2018
• Titel Quelle: Enthalten in: Gut
• Ort Quelle: London : BMJ Publishing Group, 1960
• Jahr Quelle: 2017
• Band/Heft Quelle: 66(2017), 1, Seite 137-144
• ISSN Quelle: 1468-3288
• DOI: doi:10.1136/gutjnl-2016-311739
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AUTO-ANTIBODIES
• Sach-SW: CHOLANGIOCARCINOMA
• Sach-SW: INFLAMMATORY BOWEL DISEASE
• Sach-SW: PANCREATIC ANTIBODIES
• Sach-SW: PRIMARY SCLEROSING CHOLANGITIS
• K10plus-PPN: 1580233244

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.