Anti-GBM disease (Goodpasture syndrome) occurs when autoantibodies target the non-collagenous (NC1) domain of which collagen type, and what is the specific alpha chain involved?

• A Type IV collagen, alpha-5 chain [α5(IV)] — mutated in X-linked Alport syndrome
• B Type IV collagen, alpha-3 chain [α3(IV)] — the Goodpasture antigen ✓
• C Type IV collagen, alpha-1 and alpha-2 chains — ubiquitous basement membrane components
• D Type II collagen NC1 domain — shared with collagen in vitreous and articular cartilage

Explanation

The Goodpasture antigen is the NC1 domain of the alpha-3 chain of type IV collagen [α3(IV)NC1]. This chain is expressed predominantly in the glomerular and alveolar basement membranes, explaining the dual organ targeting (pulmonary hemorrhage and crescentic glomerulonephritis) in Goodpasture syndrome. α5(IV) mutations cause X-linked Alport syndrome but α5(IV) is not the target of anti-GBM antibodies. The α3(IV) trimer is embedded within the GBM in a conformation where the NC1 epitope is normally cryptic, exposed perhaps by oxidative stress.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.