A kidney biopsy from a 35-year-old woman with nephrotic syndrome shows thickened glomerular basement membranes with 'spike and dome' pattern on silver stain and granular IgG and C3 deposits on IF. Electron microscopy shows subepithelial deposits. The pathogenesis of primary membranous nephropathy most commonly involves autoantibodies against which target?

• A Alpha-actinin-4 in the glomerular basement membrane
• B Collagen IV in the GBM (anti-GBM disease)
• C M-type phospholipase A2 receptor (PLA2R) on podocytes ✓
• D Nephrin in the slit diaphragm of podocytes

Explanation

Primary (idiopathic) membranous nephropathy is caused in ~70–80% of cases by IgG4 autoantibodies against M-type phospholipase A2 receptor (PLA2R) expressed on podocytes. These in-situ immune complexes activate complement via the lectin or alternative pathway, generating C5b-9 MAC that injures podocytes without nephritic inflammation. PLA2R serology aids in distinguishing primary from secondary forms. Anti-GBM antibodies cause Goodpasture syndrome (linear IF). Nephrin is crucial for slit diaphragm integrity but is not the target in membranous nephropathy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.