A 35-year-old woman presents with nephrotic syndrome. Renal biopsy shows diffuse thickening of the glomerular basement membrane with 'spike and dome' pattern on Jones silver stain. Immunofluorescence shows granular IgG and C3. Which antibody is most commonly responsible for the primary form of this disease?

• A Anti-GBM antibody targeting collagen IV alpha-3 chain
• B Anti-C1q antibody causing classical pathway activation
• C Anti-PLA2R antibody (anti-phospholipase A2 receptor) ✓
• D Anti-THSD7A antibody (thrombospondin type 1 domain 7A)

Explanation

Primary membranous nephropathy (the most common cause of nephrotic syndrome in adults) is most frequently caused by autoantibodies against the M-type phospholipase A2 receptor (PLA2R) expressed on podocytes. Anti-PLA2R IgG4 antibodies are found in approximately 70–75% of primary membranous nephropathy cases and can be used for non-invasive diagnosis and monitoring. Anti-THSD7A accounts for ~5% of cases. Anti-GBM is associated with Goodpasture syndrome with nephritic, not nephrotic, presentation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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