1. Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis
- Author
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Stefanie Derer, Swantje Mindorf, Marc Ehlers, Mette Vesterhus, Bianca Teegen, Hendrik Lehnert, Tobias Korf, Peter Schemmer, Florian Bär, Maike Anna Michaels, Thomas Nitzsche, Christoph M. Hammers, Laila Widmann, Lars Komorowski, Christian Sina, Johannes R. Hov, Daniel Gotthardt, Sebastian Torben Jendrek, Klaus Fellermann, Karl Heinz Weiss, Torsten Schröder, Tom H. Karlsen, and Evaggelia Liaskou
- Subjects
0301 basic medicine ,medicine.medical_specialty ,endocrine system diseases ,Autoimmune hepatitis ,Disease ,digestive system ,Gastroenterology ,Primary sclerosing cholangitis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,biology ,business.industry ,digestive, oral, and skin physiology ,Autoantibody ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Immunology ,Cohort ,biology.protein ,Secondary sclerosing cholangitis ,030211 gastroenterology & hepatology ,Bile Duct Diseases ,Antibody ,business - 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. The final version of this research has been published in Hepatology. © 2016 Wiley
- Published
- 2016