In membranoproliferative glomerulonephritis (MPGN) type II (Dense Deposit Disease), the 'tram-track' appearance on PAS stain and massive mesangial/subendothelial dense deposits are caused by uncontrolled activation of which complement pathway?

• A Classical complement pathway via immune complex deposition
• B Lectin complement pathway via MBL deficiency
• C Alternative complement pathway — C3 nephritic factor stabilizing C3 convertase ✓
• D Terminal complement pathway with excess C5-9 deposition

Explanation

Dense deposit disease (MPGN type II) is caused by uncontrolled activation of the alternative complement pathway. C3 nephritic factor (C3NeF) is an autoantibody that stabilizes the alternative pathway C3 convertase (C3bBb), preventing its normal decay and causing persistent C3 consumption. This results in very low serum C3 (with normal C1q, C4 because classical pathway is not activated) and deposition of dense C3-containing material within the GBM and mesangium. Mutations in complement factor H (CFH) have a similar effect. IF shows C3 staining without Ig.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.