Immune mechanisms of glomerular injury

• Immune complex formation within the glomerulus
  • Intrinsic (fixed) glomerular antigens
    • Type IV collagen: anti-GBM disease (GN)
    • PLA2R: membranous nephropathy (NS)
  • Deposited ("planted") glomerular antigens
    • Bacterial antigens: poststreptococcal GN
    • Tumor antigens: membranous nephropathy (NS)
• Preformed immune complex deposition from the circulation
  • Endogenous antigens
    • Galactose-deficient IgA: IgA nephropathy (GN)
    • dsDNA: lupus nephritis (GN, sometimes NS)
  • Exogenous antigens
    • Viral hepatitis C or B, HIV: immune complex MPGN
    • Bacterial antigens: endocarditis-associated GN
• Neutrophil activation: minimal (pauci-) immune complex deposition
  • Neutrophil cytoplasmic antigens
    • MPO/PR3 (ANCA-associated GN)

Clinical picture determined by site of glomerular immune injury:

• NS (nephrotic syndrome): Injury to podocytes → isolated from inflammatory mediators in Bowman space/urinary side of GBM → proteinuria without inflammation
• GN (glomerulonephritis): Injury to GBM, mesangial cells, or endothelial cells (either immune- or neutrophil-mediated) → exposed to inflammatory mediators/circulatory side of GBM → glomerular hematuria & red blood cell casts; variable proteinuria