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.
- PRIMARY SCLEROSING CHOLANGITIS
- PANCREATIC ANTIBODIES
- INFLAMMATORY BOWEL DISEASE
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STJ, DG and TN should be considered as first authors. JRH and CS share senior authorship.
Twitter Follow Tobias Korf at @primary sclerosing cholangitis
Contributors STJ, JRH, MAM and CS designed the concept of the present study. DG, JRH, LW, THK, EL, TN, K-HW, PS, SM and MV acquired the data. DG, LW, JRH, STJ, TN and CS analysed and interpreted the data. STJ, JRH and CS drafted the article. SD, HL, TK, EL, MV, KF, FB, TS, LK, SM, BT, K-HW, PS, ME, CMH and THK critically revised the article for important intellectual content. All authors read and approved the final manuscript.
Funding This research work is supported by the Else-Kröner-Fresenius-Stiftung, Bad Homburg, Germany (Research grant 2013-A202 to CS). JRH is funded by the Norwegian Research Council (240787/F20). CMH is funded by the German Research Foundation (DFG, HA6736/2-1).
Competing interests LK, SM, BT and TN are employees of Euroimmun AG, Lübeck, Germany.
Ethics approval Ethical Committee of the University of Lübeck (AZ 13/084A; AZ 05-112) and the Regional Committee for Medical and Health Research Ethics South-Eastern Norway B (2011/2572) as well the Ethical Committee of the University of Heidelberg (S-043/2011).
Provenance and peer review Not commissioned; externally peer reviewed.