Cofactor activity controls complement activation. The most common functional defect in aHUS is reduced cofactor activity for C3b. (A) Cofactor activity. On the membrane of host cells, cofactors MCP and factor H bind C3b. This allows the serum protease factor I to cleave C3b and thereby prevent further C3 activation. (B) Complement regulators on cells and in plasma inhibit C3b. Mutations in one of the 3 inhibitors of the C3 and C5 convertases (factor H, factor I, and MCP) are seen in ∼ 50% of aHUS patients. MCP is widely expressed on almost all cells. Factor H, an abundant protein of plasma, is required for control in plasma and can bind to cell membranes and carry out CA. MCP and factor H both bind C3b, thereby enabling factor I to cleave C3b and thus prevent its participation in the AP's feedback loop.