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

Huugen, D., van Esch, A., Xiao, H., Peutz-Kootstra, C. J., Buurman, W. A., Tervaert, J. W. C., Jennette, J. C. & Heeringa, P., Apr-2007, In : Kidney International. 71, 7, p. 646-654 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • D. Huugen
  • A. van Esch
  • H. Xiao
  • C. J. Peutz-Kootstra
  • W. A. Buurman
  • J. W. Cohen Tervaert
  • J. C. Jennette
  • P. Heeringa

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.

Original languageEnglish
Pages (from-to)646-654
Number of pages9
JournalKidney International
Volume71
Issue number7
Publication statusPublished - Apr-2007

    Keywords

  • anti-neutrophil cytoplasmic autoantibody, glomerulonephritis, neutrophil, complement, animal model, ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES, CRESCENTIC GLOMERULONEPHRITIS, GLOMERULAR DEPOSITION, IN-VITRO, MYELOPEROXIDASE, NEUTROPHILS, VASCULITIS, ACTIVATION, ANCA, ADHESION

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