A 45-year-old woman with primary biliary cholangitis (PBC) undergoes liver biopsy. Histology shows florid duct lesion with lymphocytic infiltration of bile duct epithelium, granuloma formation around damaged ducts, and ductopenia in portal tracts. Which autoantibody has the highest specificity for PBC and targets which mitochondrial enzyme complex?
- A Anti-smooth muscle antibody (SMA) — targets F-actin; associated with autoimmune hepatitis
- B Anti-mitochondrial antibody (AMA M2) — targets E2 component of pyruvate dehydrogenase complex (PDC-E2); >95% specificity for PBC ✓
- C Anti-liver cytosol type 1 (LC-1) — targets formiminotransferase cyclodeaminase; autoimmune hepatitis type 2
- D Anti-soluble liver antigen (SLA/LP) — targets UGA suppressor tRNA-associated protein; most specific for AIH
Explanation
Anti-mitochondrial antibody (AMA), specifically the M2 subtype, targets the E2 component of the pyruvate dehydrogenase complex (PDC-E2) located on the inner mitochondrial membrane. AMA M2 is present in >95% of PBC patients with >99% specificity. The pathogenic mechanism involves aberrant PDC-E2 expression on bile duct epithelial cell surfaces under oxidative stress, triggering CD4/CD8 lymphocyte attack on cholangiocytes (immune tolerance breakdown). Ursodeoxycholic acid (UDCA) and obeticholic acid are treatments. Anti-SMA (AIH type 1), anti-LKM1 (AIH type 2), anti-SLA (most specific for AIH, poor prognosis).
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.