title: Complement Dysregulation and Disease: Insights from Contemporary Genetics.
abstract: The vertebrate complement system consists of sequentially interacting proteins that provide for a rapid and powerful host defense. Nearly 60 proteins comprise three activation pathways (classical, alternative, and lectin) and a terminal cytolytic pathway common to all. Attesting to its potency, nearly half of the system's components are engaged in its regulation. An emerging theme over the past decade is that variations in these inhibitors predispose to two scourges of modern humans. One, occurring most often in childhood, is a rare but deadly thrombomicroangiopathy called atypical hemolytic uremic syndrome. The other, age-related macular degeneration, is the most common form of blindness in the elderly. Their seemingly unrelated clinical presentations and pathologies share the common theme of overactivity of the complement system's alternative pathway. This review summarizes insights gained from contemporary genetics for understanding how dysregulation of this powerful innate immune system leads to these human diseases.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; email: j.p.atkinson@wustl.edu.
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Liszewski
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Anuja
authors.initials: A
authors.lastname: Java
authors.affiliation: Serion Inc., St. Louis, Missouri 63108.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Schramm
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; email: j.p.atkinson@wustl.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
mesh_terms: D065766:Atypical Hemolytic Uremic Syndrome / Q000503:physiopathology*; D003170:Complement Pathway, Alternative / Q000235:genetics*; D003165:Complement System Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000503:physiopathology*
chemical_list: D003165:Complement System Proteins
keywords: C3; C3 glomerulopathies; CD46; age-related macular degeneration; alternative complement pathway; atypical hemolytic uremic syndrome; factor B; factor H; factor I