Figure 4.

Comparison of uncontrolled C3 activation in CFH and combined CFH and properdin deficiency states. (A) In CFH-deficient mice, there is uncontrolled activation of both C3 and C5. As a consequence, plasma levels of both C3 and C5 are severely reduced. Uncontrolled activation of C3 results in the generation of C3b fragments such as iC3b, a process that is dependent on the enzyme factor I. We have previously shown that the absence of either factor B or factor I but not C5 prevented the accumulation of C3 along the GBM. (B) In CFH-deficient mice lacking properdin uncontrolled C3 activation persists, whereas plasma C5 depletion, although present, is less severe (thinner arrow). Glomerular C3 accumulation is increased in these animals. One explanation could be that reduced C3b utilization by the C5 convertase increases the amount of C3b that could be cleaved to iC3b and deposit along the GBM.