Membranoproliferative glomerulonephritis type II (Dense Deposit Disease) is characterised by electron-dense deposits within the glomerular basement membrane (intramembranous). Which complement pathway abnormality is MOST responsible for its pathogenesis?

• A Anti-C1q antibodies activate excessive classical pathway complement
• B C3 nephritic factor (C3NeF) IgG antibody stabilises the alternative pathway C3 convertase (C3bBb) ✓
• C Deficiency of mannose-binding lectin causing unopposed lectin pathway activation
• D Homozygous C4 deficiency leading to defective clearance of immune complexes

Explanation

Dense Deposit Disease (MPGN type II) is driven by uncontrolled alternative pathway activation; C3 nephritic factor is an IgG autoantibody that binds and stabilises the C3bBb convertase, preventing its decay and causing persistent C3 consumption. This leads to hypocomplementaemia (low C3, normal C4) and dense osmiophilic deposits within the GBM on EM.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.