In C3 glomerulopathy (C3G), which distinguishes the two main entities — dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) — by electron microscopy and the underlying pathomechanism?

• A DDD shows large hump-shaped subepithelial deposits (as in post-infectious GN); DDD is caused by anti-GBM antibody deposition
• B DDD shows highly electron-dense, ribbon-like, osmiophilic deposits within the GBM lamina densa; DDD is more commonly associated with C3 nephritic factor (C3NeF) or factor H mutation causing alternative complement pathway dysregulation ✓
• C C3GN shows mesangial-only deposits without capillary wall involvement; it requires no treatment
• D Both DDD and C3GN are distinguished only by light microscopy showing diffuse vs. focal patterns; EM findings are identical

Explanation

C3 glomerulopathy encompasses DDD and C3GN, both caused by uncontrolled activation of the alternative complement pathway (C3 hyperactivation), evidenced by dominant C3 staining with absent or trace immunoglobulin on immunofluorescence. DDD is characterized by electron-dense, ribbon-like, highly osmiophilic deposits within the GBM lamina densa (intramembranous), which is pathognomonic. C3GN shows mesangial and subendothelial deposits without this distinctive lamina densa transformation. Both entities may have C3NeF (stabilizes C3 convertase C3bBb), factor H deficiency/mutation, factor I deficiency, or anti-factor H antibodies. The critical distinguishing EM feature is the lamina densa-replacing osmiophilic material unique to DDD.

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

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Written and medically reviewed by the StethoPrep medical team.