In anti-GBM disease (Goodpasture syndrome), the autoantibodies target the α3 chain of type IV collagen in the GBM. The Goodpasture antigen is normally cryptic (not exposed to immune system). Which event is thought to UNMASK this antigen and trigger the autoimmune response?

• A Molecular mimicry with streptococcal M protein
• B Complement C3 deposition activating alternative pathway
• C Cigarette smoke, inhaled hydrocarbons, or infections (e.g., influenza) that alter GBM architecture and expose the α3NC1 domain ✓
• D Loss of regulatory T cells allowing autoreactive B cells to escape tolerance

Explanation

The α3 chain NC1 domain of type IV collagen is normally sequestered within the GBM superstructure (hexamers held by disulfide bonds) and is not accessible to the immune system. Environmental triggers — particularly cigarette smoking, solvent/hydrocarbon inhalation, and respiratory infections including influenza — are thought to disrupt this superstructure, exposing the cryptic α3NC1 epitope. This unmasking, in genetically susceptible individuals (HLA-DR15), triggers autoantibody production. The linear IgG deposits on IF and the simultaneous pulmonary hemorrhage (capillary basement membrane shares the antigen) confirm anti-GBM disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.