A 45-year-old woman with longstanding hepatitis C infection presents with nephrotic-range proteinuria and hypocomplementemia (low C3 and C4). Cryoglobulins are detected in serum. Renal biopsy shows a lobular 'tram-track' pattern on silver stain. What is the underlying mechanism of glomerular injury?
- A T-cell mediated cytotoxicity against podocytes
- B Anti-GBM antibody formation cross-reacting with hepatitis C antigens
- C Deposition of immune complexes containing HCV antigens and cryoglobulins causing complement activation ✓
- D Direct viral infection of glomerular endothelial cells
Correct answer: C. Deposition of immune complexes containing HCV antigens and cryoglobulins causing complement activation
Explanation
Membranoproliferative glomerulonephritis (MPGN) type I associated with hepatitis C infection results from deposition of cryoglobulin-containing immune complexes (HCV antigens, IgG, IgM rheumatoid factor) in the mesangium and subendothelial space, activating the classical complement pathway and lowering both C3 and C4. The tram-track appearance on silver stain reflects mesangial cell interposition and glomerular basement membrane duplication. Anti-GBM antibodies cause Goodpasture syndrome; direct viral infection of podocytes is the mechanism in HIVAN.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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