A 40-year-old man with hepatitis C infection presents with proteinuria, hematuria, and low C3. Renal biopsy shows mesangial and endocapillary hypercellularity with a 'tram-track' appearance on silver stain. Immunofluorescence shows IgM, IgG, C3 deposits. The pathogenetic mechanism most specific to this entity is:
- A Anti-GBM antibody deposition activating complement via classical pathway
- B Podocyte effacement by T-cell-derived permeability factor
- C Deposition of cryoglobulins (type II mixed cryoglobulinemia) with HCV-IgG immune complexes activating complement ✓
- D Activation of alternative complement pathway by CFHR5 mutation
Explanation
This is membranoproliferative glomerulonephritis (MPGN) pattern on biopsy — the 'tram-track' appearance results from GBM duplication due to mesangial interposition. In the context of hepatitis C, the dominant mechanism is type II mixed cryoglobulinemia: HCV antigen drives B-cell clonal expansion producing monoclonal IgM with rheumatoid factor activity that complexes with HCV-IgG to form cryoglobulins (IgM-IgG immune complexes). These precipitate in glomerular capillaries and activate complement via the classical pathway, causing the MPGN pattern and low C3. Anti-GBM antibodies cause linear IF and crescentic GN (Goodpasture); permeability factors cause podocytopathy (minimal change/FSGS); CFHR5 mutations cause C3 glomerulopathy with C3-dominant deposits.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.