Autoantibodies in haemolytic uraemic syndrome (HUS).
Haemolytic uraemic syndrome (HUS) is a severe disease with renal failure, microangiopathic anemia and thrombocytopenia. Several mechanisms leading to HUS have been identified, like infections with enterohaemorrhagic Escherichia coli, as well as genetic mutations of complement genes, which result in defective complement control on the surface of host cells. The complement system forms the first defense line of innate immunity and mediates the attack against foreign microorganisms. Defective regulation of this cascade results in attack of self cells and in autoimmune disease. Apparently, the alternative pathway convertase C3bBb is central for the pathophysiology of HUS as gene mutations of the components (C3 and Factor B) or of regulators (Factor H, Factor I and MCP/CD46) are observed in the genetic form of HUS. Recently, a novel mechanism leading to atypical HUS (aHUS) was identified, in form of autoantibodies that bind the complement inhibitor Factor H. Here we summarize the current concept of HUS and focus in particular on the novel subgroup of aHUS patients with IgG autoantibodies to Factor H which develop on the genetic background of CFHR1/CFHR3 deficiency, and which define a new subform termed DEAP-HUS (deficient for CFHR proteins and Factor H autoantibody positive).
Skerka
Christine
C
Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstr 11a, 07745 Jena, Germany. christine.skerka@hki-jena.de
Józsi
Mihály
M
Zipfel
Peter F
PF
Dragon-Durey
Marie-Agnes
MA
Fremeaux-Bacchi
Veronique
V
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins / Q000172:deficiency / Q000235:genetics; D017242:Complement Factor H / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008822:Mice, Transgenic; D010375:Pedigree; D017434:Protein Structure, Tertiary
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D017242:Complement Factor H