MPGN II is a
rare disease which is characterized by
complement containing deposits within the GBM. The disease is characterized by functional impairment of the GBM causing progressive loss of renal function eventually resulting in
end stage renal disease. It now becomes evident that in addition to C3NeF, which inhibits the inactivation of the alternative
C3 convertase C3bBb, different genetically determined factors are also involved in the pathogenesis of MPGN II. These factors though different from C3NeF also result in defective
complement regulation acting either through separate pathways or synergistically with C3NeF. Following the finding of MPGN II in
Factor H deficient animals, patients with MPGN II were identified presenting with an activated
complement system caused by
Factor H deficiency.
Factor H gene mutations result in a lack of plasma
Factor H or in a functional defect of
Factor H protein. Loss of
Factor H function can also be caused by inactivating
Factor H autoantibodies, C3 mutations preventing interaction between C3 and
Factor H, or
autoantibodies against C3. Identification of patients with MPGN II caused by defective
complement control may allow treatment by replacement of the missing factor via plasma infusion, thus possibly preventing or at least delaying disease progress.