Kidney Diseases Caused by Complement Dysregulation: Acquired, Inherited, and Still More to Come

Figure 1

Dysregulation of the alternative complement cascade due to acquired or genetic factors leads to defective complement control causing a range of complement-associated glomerulopathies. C3 is cleaved to generate C3a and C3b. After binding of C3b to factor B, the complex is cleaved by factor D to form C3-convertase. The initial convertase constantly cleaves C3 at a low rate (referred to as “tick-over” of the alternative pathway). Binding of another C3b-fragment to C3-convertase creates a C5-convertase after which the pathway proceeds in the same manner as the classical pathway recruiting additional complement factors to ultimately form the membrane attack complex (MAC). The alternative pathway is strictly regulated by complement regulating proteins (listed in red). Mutations, genetic variations, or antibodies against complement regulating proteins or C3-convertase lead to abnormal C3-convertase activity. The subsequent deposition of activated complement products causes a range of complement-associated glomerulopathies. Abbreviations: C3; complement component 3, CFHR3; complement factor H related protein, AP; alternative pathway.