Membranoproliferative glomerulonephritis (MPGN) type II (dense deposit disease) is characterised by intramembranous dense deposits and low C3 complement levels with normal C1q and C4. What is the primary mechanism of complement dysregulation in dense deposit disease?

• A Deficiency of C1-inhibitor causing uncontrolled classical pathway activation
• B Mutations in mannose-binding lectin causing lectin pathway over-activation
• C Autoantibody against C4b blocking classical pathway regulation
• D C3 nephritic factor (C3NeF) — an IgG autoantibody that stabilises and prevents decay of the alternative pathway C3 convertase (C3bBb) ✓

Explanation

Dense deposit disease (MPGN type II) is driven by alternative complement pathway dysregulation. C3 nephritic factor (C3NeF) is an IgG autoantibody that binds to the alternative pathway C3 convertase (C3bBb) at its properdin-binding site, stabilising it against factor H-mediated decay and prolonging its half-life dramatically. This causes continuous alternative pathway activation, depleting C3 without consuming C1q or C4 (classical pathway intact). The resulting low C3/normal C1q and C4 pattern is diagnostically distinctive. Mutations in factor H or CFH also cause similar complement dysregulation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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