Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice

Kidney Int. 2007 Apr;71(7):646-54. doi: 10.1038/ Epub 2007 Feb 14.


In mice, administration of murine anti-myeloperoxidase (MPO) IgG induces pauci-immune necrotizing crescentic glomerulonephritis. Recent studies in this model indicate a crucial role for complement activation in disease induction. Here, we investigated the effect of pretreatment or intervention with a C5-inhibiting monoclonal antibody (BB5.1) in the mouse model of anti-MPO IgG-induced glomerulonephritis. Mice received BB5.1 8 h before or 1 day after disease induction with anti-MPO IgG and lipopolysaccharide. Mice were killed after 1 or 7 days. Control antibody-pretreated mice developed hematuria, leukocyturia and albuminuria, and glomerulonephritis with a mean of 21.0+/-8.8% glomerular crescents and 12.8+/-5.5% glomerular capillary necrosis. BB5.1 pretreatment prevented disease development, as evidenced by the absence of urinary abnormalities, a marked reduction in glomerular neutrophil influx at day 1 and normal renal morphology at day 7. Importantly, BB5.1 administration 1 day after disease induction also resulted in a marked attenuation of urinary abnormalities and a more than 80% reduction in glomerular crescent formation. In conclusion, inhibition of C5 activation attenuates disease development in a mouse model of anti-MPO IgG-induced glomerulonephritis. These results favor further investigations into the role of complement activation in human MPO-anti-neutrophil cytoplasmic autoantibody-mediated glomerulonephritis, and indicate that inhibition of C5 activation is a potential therapeutic approach in this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Complement C5 / antagonists & inhibitors*
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / prevention & control
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / immunology*


  • Complement C5
  • Immunoglobulin G
  • Peroxidase