A 35-year-old woman presents with rapidly progressive glomerulonephritis. Renal biopsy shows crescentic glomerulonephritis. Immunofluorescence: linear IgG along the glomerular basement membrane. Anti-GBM antibodies are detected in serum. What is the specific target antigen for these antibodies?

• A Laminin beta-2 chain in the GBM
• B Podocin in podocyte slit diaphragm
• C Alpha-3 chain of type IV collagen (alpha-3(IV)NC1 domain) ✓
• D Phospholipase A2 receptor (PLA2R) on the GBM

Explanation

Anti-GBM disease (Goodpasture syndrome) is caused by autoantibodies directed against the non-collagenous domain 1 (NC1) of the alpha-3 chain of type IV collagen [α3(IV)NC1], which is uniquely expressed in the GBM and pulmonary alveolar basement membrane. This explains the dual renal-pulmonary involvement. Linear IgG on IF is pathognomonic. PLA2R is the antigen in primary membranous nephropathy. Podocin mutations cause hereditary nephrotic syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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