Atypical hemolytic uremic syndrome caused by primary complement defects

Complement is one of the most archaic parts of the innate immune system, which enhances the ability of antibodies and phagocytic cells to clear cell debris, and microorganisms. The complement system promotes inflammation and attacks the pathogen's plasma membrane. Malfunction of the system may lead to the development of autoimmunity or uncontrolled infections. Further, dysregulation of the tightly controlled complement activation process may lead to thrombotic microangiopathies with consequent multiorgan involvement. The present paper gives a short overview of the different pathways of complement activation. It focuses on primary genetic defects of components of the alternative pathway that result in dysregulation as well as on pathomechanism, classification, diagnostics and treatment of atypical hemolytic uremic syndrome (aHUS) based on the most recent international recommendations and guidelines. Finally the critical role of complement in host immunity and genetic diagnostics of complement deficiencies are illustrated with two cases of aHUS.