C3 glomerulopathy (C3G) is defined by glomerular C3 deposits with absent or minimal immunoglobulin deposits on immunofluorescence. The unifying pathogenetic mechanism across all C3G variants is:

• A Immune complex deposition with secondary complement activation
• B Overactivation of the lectin pathway via MBL polymorphisms
• C Anti-C1q antibodies blocking classical pathway inhibition
• D Dysregulation of the alternative complement pathway in the fluid phase ✓

Explanation

C3 glomerulopathy (dense deposit disease and C3 GN) is caused by dysregulation of the alternative complement pathway specifically in the fluid phase, leading to excessive C3 cleavage and C3 fragment deposition in glomeruli. Causes include: C3 nephritic factor (C3NeF) — an IgG autoantibody that stabilizes the alternative pathway C3 convertase (C3bBb) by preventing Factor H binding; genetic mutations in complement regulatory proteins (Factor H, Factor I, Factor B, C3); and Factor H autoantibodies. The result is persistent alternative pathway overactivation with C3 consumption (low serum C3) and C3 fragment deposition without Ig. Lectin pathway dysregulation and classical pathway mechanisms result in immune complex GN with Ig deposits.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.