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. Cohen; Jennette, J. C.; Heeringa, P.
April 2007
Kidney International;Apr2007, Vol. 71 Issue 7, p646
Academic Journal
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.Kidney International (2007) 71, 646–654. doi:10.1038/sj.ki.5002103; published online 14 February 2007


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