C3 Glomerulopathy

C3 glomerulopathy is a broad term encompassing-

• dense deposit disease (DDD), former MPGN type II
• C3 glomerulonephritis

C3 glomerulopathy cases have low serum C3 levels (hypocomplementemia).

C3 glomerulonephritis comprises examples of MPGN types I and III, in which immunofluorescence reveals predominant C3 deposits.

Light microscopy 

Both C3GN and DDD have similar Light microscopy findings.

• Hypercellular, Lobulated glomeruli
• Duplicated basement membranes in capillary walls
• ↑↑ Mesangial matrix

Immunofluorescence – Similar in both C3GN and DDD

Bright mesangial and glomerular capillary wall staining for C3. Immunoglobulins (IgG) are absent.

Electron Microscopy – (different electron dense pattern)

C3GN

Mesangial and subendothelial electron-dense “waxy” deposits of C3.

DDD 

lamina densa and subendothelial space of the GBM are transformed into an irregular, ribbonlike, and extremely electron-dense structure.

Pathogenesis 

The following is commonly associated with upregulated alternative complement pathway -

• Autoantibodies that stabilize C3 convertase -C3NeF (C3 Nephritic factors)
• Mutation in complement regulatory protein genes

• • Factor H
  • Factor I
  • MCP

Acquired or hereditary abnormality of the alternative pathway of complement system→ Unregulated activation of Alternative Pathway (antibody-independent pathway) → Increased Inflammation and inflammatory mediators → Glomerular Injury → ESRD

Clinical features 

DDD cases present at younger ages. And the onset of disease in C3GN is generally around older age.

Common in both C3GN and DDD

• Hematuria
• Proteinuria
• Renal Insufficiency

Most commonly associated with DDD

• Ocular drusen (yellow deposits in the retina)
• Acquired Partial lipodystrophy

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