A 30-year-old woman with nephrotic syndrome has renal biopsy showing diffuse thickening of GBM with 'spike and dome' pattern on Jones methenamine silver stain. Electron microscopy shows subepithelial electron-dense deposits with spikes of basement material between deposits. Immunofluorescence shows granular deposits of IgG and C3 along capillary walls. The most specific pathogenic mechanism identified in primary membranous nephropathy is autoantibodies against:
- A Glomerular basement membrane collagen
- B Neutrophil cytoplasmic antigens
- C Phospholipase A2 receptor (PLA2R) ✓
- D Double-stranded DNA
Correct answer: C. Phospholipase A2 receptor (PLA2R)
Explanation
Approximately 70-80% of primary membranous nephropathy cases involve autoantibodies against the M-type phospholipase C2 receptor (PLA2R) on podocytes. This discovery transformed understanding of the disease. ANCA is associated with pauci-immune crescentic GBM. Anti-GBM antibodies target type IV collagen in Goodpasture disease. Anti-dsDNA is characteristic of lupus nephritis.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.