A kidney biopsy shows linear IgG deposition along the glomerular basement membrane (GBM) on immunofluorescence with no electron-dense deposits. The patient has anti-GBM antibodies. The epitope targeted by pathogenic antibodies in anti-GBM (Goodpasture) disease resides in:

• A The triple-helical collagenous domain of alpha1 chain of type IV collagen
• B Nephrin, a transmembrane protein of the slit diaphragm between podocyte foot processes
• C The non-collagenous-1 (NC1) domain of the alpha3 chain of type IV collagen (alpha3[IV]NC1) ✓
• D Laminin-521, a component of the GBM lamina densa adjacent to podocyte foot processes

Explanation

Goodpasture disease (anti-GBM nephritis) is caused by IgG autoantibodies targeting the NC1 domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1]. Type IV collagen is the major structural component of the GBM. The alpha3 chain NC1 domain is normally cryptic (hidden within the NC1 hexamer) but becomes exposed through oxidative modification or genetic susceptibility. These antibodies also bind the NC1 domain of alpha3(IV) collagen in the alveolar basement membrane, explaining pulmonary hemorrhage. The triple-helical domain is not the target. Nephrin is the target of congenital nephrotic syndrome (Finnish type) due to NPHS1 mutations. Laminin-521 mutations cause pierson syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.