CD59 protects glomerular endothelial cells from immune-mediated thrombotic microangiopathy in rats.

CD59 is a cell membrane-bound complement regu- latory protein on glomerular cells that inhibits C5b-9 assembly and insertion. This report describes a recently developed model of immune thrombotie mieroangiopathy (TMA) induced by the renal artery perfusion of anti-glomerular endothelial cell (anti- GEN) antibody. To examine the role of CD59 in protecting the GEN from immune-mediated injury, rats underwent selective renal artery perfusion with F(ab')2 fragments of anti-CD59 monoclonal antibody to block CD59 activity or control mouse IgO followed by anti-OEN antibody or control goat IgG. Neutralization of CDS9 in normal rats did not result in any significant functional or histologic changes. Perfusion with anti-CDS9 did not change deposition of the pathogenic anti- GEN IgO used to induce the TMA model. However, neutral- ization of CDS9 in the TMA model resulted in more C5b-9 formation in glomeruli, accompanied by increased platelet and fibrin deposition, more severe endothelial injury, and reduced renal function compared with the animals perfused with control F(ab')2 fragments. These results demonstrate directly that CDS9 serves a protective role for GEN in this TMA model of rats, and confirm that C5b-9 formation has a critical pathogenic role in the mediation of the disease. CDS9 may play an im- portant role in protecting glomerular endothelium from other complement-mediated types of injury. (J Am Soc Nephrol 9: