A 50-year-old woman with primary biliary cholangitis (PBC) has AMA (anti-mitochondrial antibody) positivity and liver biopsy showing florid duct lesion with granulomatous inflammation around bile ducts. The target antigen of AMA in PBC is located in which cellular compartment?

• A Biliary epithelial cell surface nuclear pore complex
• B Smooth muscle actin in hepatocyte cytoskeleton
• C Liver-kidney microsomal antigen (LKM-1) in hepatocyte ER
• D Cytoplasmic inner mitochondrial membrane — pyruvate dehydrogenase complex E2 subunit (PDC-E2) ✓

Explanation

Anti-mitochondrial antibodies (AMA) in PBC are directed against the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) located on the inner mitochondrial membrane, specifically the lipoamide-bearing domain. This antigen is aberrantly expressed on the apical surface of biliary epithelial cells (cholangiocytes) in PBC, making them targets for immune attack. AMA-M2 (anti-PDC-E2) is the most specific diagnostic marker for PBC, present in ~95% of cases. LKM-1 antibodies are seen in autoimmune hepatitis type 2.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.