A 40-year-old man with primary sclerosing cholangitis (PSC) and IBD undergoes ERCP showing 'beaded' appearance of intra- and extrahepatic bile ducts. Liver biopsy shows periductal 'onion-skin' fibrosis. The characteristic bile duct lesion and its biliary epithelial cell destruction is mediated primarily by:

• A IgG4-positive plasma cell infiltration causing IgG4-associated cholangitis — distinct from PSC
• B Copper accumulation in biliary epithelium causing direct toxic injury
• C CMV-mediated biliary epithelial destruction in immunocompromised patients
• D CD4+ T-cell-mediated periductal fibrosis with HLA-B8, DR3 genetic susceptibility driving aberrant biliary expression of HLA class II ✓

Explanation

PSC is an autoimmune-mediated progressive fibro-inflammatory cholangiopathy strongly associated with HLA-B8, DR3 haplotype and UC (70-80% of PSC cases). Aberrant HLA class II expression on biliary epithelial cells allows them to present self-antigens to autoreactive CD4+ T-cells, triggering periductal inflammation and the pathognomonic 'onion-skin' concentric periductal fibrosis. IgG4-associated cholangitis (IAC) mimics PSC but shows dense IgG4+ plasma cell infiltrates and responds to steroids — a critical differential diagnosis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.