Disease specific alterations of the bile-duct derived biliary proteome in primary sclerosing cholangitis

Background and aims: Bile proteomic analysis in primary sclerosing cholangitis (PSC) revealed already disease activity and malignancy specific alterations. We aimed to establish a reference bile-duct derived bile proteome of PSC in absence of infectious or malignant conditions to provide insight into underlying biliary pathophysiology.

Methods: Bile duct-derived bile samples were collected from PSC patients without signs of bacterial cholangitis (n = 6) or patients with choledocholithiasis (n = 6, the control group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to analyse the proteins, 2-D-gel patterns were compared by densitometry and difference gel electrophoresis (DIGE).

Results: We identified 425 proteins in bile fluid of PSC patients. 101 proteins were only present in PSC patients but not in controls. 61 of these proteins have not been described in bile before. Analysis of predicted localization and pathways revealed an elevation of intracellular proteins, especially of the ribosomal and proteasomal pathways in PSC patients, e.g PSME2. On the contrary we identified 91 proteins that were only found in bile fluid of controls. Of those higher proportion was derived from the extracellular space with predominantly cell adhesion, complement and coagulation cascade functions, like COL1A1 and ICAM1. In addition from the proteins found in both groups 10 proteins were at least 10 times upregulated (e.g. ENPL) and 23 proteins were at least ten time downregulated (e.g. CBPB1) in PSC.

Conclusions: The bile-duct bile proteome of patients with PSC comprises disease specific alterations with inflammation-associated protein pattern even in absence of clinical obvious signs of cholangitis.