Atypical hemolytic uremic syndrome.
OBJECTIVE
The last few years revealed a molecular distinction between thrombotic thrombocytopenic purpura, a disease characterized by a lack of ADAMTS13 activity, and atypical hemolytic uremic syndrome (aHUS), a disease of complement overactivation. Many different predisposing genetic factors resulting in complement overactivation have been described in aHUS. Additionally, autoantibodies against complement regulatory proteins have been reported.


RESULTS
The last year has seen the description of a new risk factor for aHUS in the form of mutations in thrombomodulin. As with other genetic risk factors seen in aHUS, these mutations result in impaired regulation of complement. It is increasingly recognized that a confluence of risk factors resulting in complement overactivation may be required for the disease to manifest. In the last year the complement inhibitor eculizumab has been used successfully to treat patients with aHUS.


CONCLUSIONS
The characterization of the molecular defect in aHUS has allowed targeted therapy to be used. Although early reports of the efficacy of the complement inhibitor eculizumab are promising, the outcome of a recent clinical trial is awaited.
Kavanagh
David
D
The Institute of Human Genetics, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK. david.kavanagh@ncl.ac.uk
Goodship
Timothy H J
TH
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D003167:Complement Activation / Q000235:genetics / Q000276:immunology*; D017242:Complement Factor H / Q000172:deficiency / Q000235:genetics; D051056:Complement Inactivating Agents / Q000627:therapeutic use; D006463:Hemolytic-Uremic Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D010951:Plasma Exchange; D019851:Thrombophilia
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; C493495:CFH protein, human; D051056:Complement Inactivating Agents; D017242:Complement Factor H; C481642:eculizumab