title: Complement regulators in human disease: lessons from modern genetics.
abstract: First identified in human serum in the late 19th century as a 'complement' to antibodies in mediating bacterial lysis, the complement system emerged more than a billion years ago probably as the first humoral immune system. The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function-altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating 'hyperinflammatory complement phenotypes'. To treat these 'complementopathies', a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. Additional therapeutic reagents are on the horizon.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Liszewski
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Atkinson
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001796:Blood Protein Disorders / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D003167:Complement Activation / Q000235:genetics / Q000276:immunology / Q000502:physiology; D017242:Complement Factor H / Q000235:genetics; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors; D003165:Complement System Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology; D006801:Humans; D008268:Macular Degeneration / Q000276:immunology; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015938:Complement Membrane Attack Complex; D017242:Complement Factor H; D003165:Complement System Proteins
keywords: age-related macular degeneration; atypical haemolytic uraemic syndrome; complement regulation; eculizumab; genetics; therapeutics