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Objectives Methods Results Conclusions Patients diagnosed with primary sclerosing cholangitis (PSC) but with characteristics of immunoglobulin G4 (IgG4)‐associated cholangitis (IAC) have been described. IAC often presents with biliary IgG4‐positive plasma cell (IgG4+ PC) infiltration and responds to corticosteroids. In PSC, the frequencies or implications of biliary IgG4+ PC are unknown. We aimed to characterize the phenomenon of biliary IgG4+ PC in patients with an established PSC diagnosis.Bile duct biopsies from 191 surveillance or therapeutic endoscopic retrograde cholangiography of 58 PSC patients were retrospectively analyzed for IgG4+ PC infiltration. Patients with ≥10 IgG4+ PC per high‐power field (HPF) were identified and characterized by clinical parameters, including serum IgG4 and cholangiographic presentations.Altogether 39.7% of the PSC patients showed ≥10 IgG4+ PC/HPF in bile duct biopsies. Patients with biliary IgG4+ PC infiltration were significantly younger at diagnosis of PSC (P = 0.023). There was no association between biliary IgG4+ PC infiltration and transplant‐free survival (P = 0.618). Patients with IgG4+ PC infiltration in bile duct biopsies showed significantly higher baseline (P = 0.002) and maximum (P = 0.001) serum IgG4 compared to those without. Biliary IgG4+ PC infiltration was associated with high‐grade bile duct strictures (P = 0.05). IgG4‐positive plasma cell infiltrations were found multifocally in 72.7% of this subgroup of PSC patients.IgG4+ PC ≥10/HPF can be found abundantly in bile duct biopsies in PSC. Histological findings correlated with serum IgG4, age, and high‐grade bile duct strictures. IgG4+ PC was located multifocally, hinting at a systemic biliary phenotype. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra‐ and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin‐6 (IL‐6)‐dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4+ TH1 and TH17 cells in PSC. The IL‐6/STAT3 pathway was shown to be regulated by protease‐activated receptor 1 (PAR1) contributing to inflammation. The role of the PAR1 −506 deletion/insertion (Del/Ins) polymorphism in PSC has not yet been investigated.Two hundred eighty four PSC patients (200 patients with inflammatory bowel diseases [IBD] and 84 without IBD) and 309 healthy controls were genotyped for PAR1 rs11267092 (−506 Del/Ins −13 bp). Results were correlated with clinical characteristics and transplant‐free survival.The frequency of PAR1 –506 Ins allele carriers (Del/Ins and Ins/Ins) was significantly higher in PSC patients (57.0%) compared to healthy controls (39.8%). Furthermore, carriers of PAR1 −506 Ins allele were more likely to have PSC than noncarriers (odds ratio 2.01; 95% confidence interval, 1.45–2.79). Patients with PSC carrying the PAR1 −506 Ins allele showed significantly higher alanine aminotransferase serum levels (p = 0.0357) and a trend toward shorter transplant‐free survival time compared to noncarriers (8.9 ± 6.6 years vs. 10.5 ± 7.1 years; p = 0.076).Our study shows that PAR1 −506 Ins is significantly more frequent in people with PSC. As PAR1 −506 Ins allele carriers tended to have a shorter transplant‐free survival, PAR1 might play a role in the development and course of PSC. [ABSTRACT FROM AUTHOR]