A 30-year-old man with hemoptysis, dyspnea, and hematuria has diffuse pulmonary hemorrhages and focal glomerular necrosis with crescents; immunofluorescence shows linear deposition of IgG and C3 along the glomerular basement membrane. Which mechanism underlies his kidney disease?

A 30-year-old man with hemoptysis, dyspnea, and hematuria has diffuse pulmonary hemorrhages and focal glomerular necrosis with crescents; immunofluorescence shows linear deposition of IgG and C3 along the glomerular basement membrane. Which mechanism underlies his kidney disease?

• A. ANCA-associated vasculitis
• B. Immune complex deposition
• C. Anti-dsDNA antibodies
• D. Anti-GBM antibody–mediated disease

Answer: (D)

Autoimmune attack on basement membranes in the kidney and lungs. The linear pattern of IgG and C3 along the glomerular basement membrane shows that antibodies are directly targeting the basement membrane itself, specifically type IV collagen. These anti-GBM antibodies bind to GBM and alveolar basement membranes, activate complement, and recruit inflammatory cells, leading to necrotizing glomerulonephritis with crescents and pulmonary hemorrhage. This linear deposition contrasts with immune complex diseases (which are granular on immunofluorescence) and with ANCA-associated vasculitis (which is pauci-immune with little deposition). Anti-dsDNA is associated with immune complex–mediated damage in SLE, not linear GBM staining. Thus the mechanism is anti-GBM antibody–mediated destruction of basement membranes.

Autoimmune attack on basement membranes in the kidney and lungs. The linear pattern of IgG and C3 along the glomerular basement membrane shows that antibodies are directly targeting the basement membrane itself, specifically type IV collagen. These anti-GBM antibodies bind to GBM and alveolar basement membranes, activate complement, and recruit inflammatory cells, leading to necrotizing glomerulonephritis with crescents and pulmonary hemorrhage. This linear deposition contrasts with immune complex diseases (which are granular on immunofluorescence) and with ANCA-associated vasculitis (which is pauci-immune with little deposition). Anti-dsDNA is associated with immune complex–mediated damage in SLE, not linear GBM staining. Thus the mechanism is anti-GBM antibody–mediated destruction of basement membranes.