Primary sclerosing cholangitis with IgG4‐positive plasma cells in bile duct biopsies ― Frequency and characterization

Objectives 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. Methods 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. Results 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. Conclusions 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.