The role of defective complement control in hemolytic uremic syndrome.
Atypical hemolytic uremic syndrome (HUS) is a severe disease that is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Recent evidence has shown that defective complement activation and defective complement control is a cause of HUS. So far, mutations in single genes coding for the cofactor and complement regulator factor H, the membrane cofactor protein (MCP/CD46), the serine protease factor I, and autoantibodies to factor H have been linked to HUS. All of these proteins affect the same enzyme the alternative pathway convertase C3bBb. This article explains how alternative pathway activation proceeds and how defective control increases activation, which ultimately leads to endothelial cell damage.
Zipfel
Peter F
PF
Department of Infection Biology, Leibniz-Institute for Natural Product Research, Jena, Germany. peter.zipfel@hki-jena.de
Misselwitz
Joachim
J
Licht
Christoph
C
Skerka
Christine
C
D017242:Complement Factor H / Q000235:genetics; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000378:metabolism*; D005340:Fibrinogen / Q000235:genetics; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051916:Membrane Cofactor Protein / Q000235:genetics; D008954:Models, Biological; D009154:Mutation
C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D017242:Complement Factor H; D005340:Fibrinogen; D003165:Complement System Proteins