Update on evaluating complement in hemolytic uremic syndrome.
OBJECTIVE
The last few years have seen the decoding of the genetic basis for atypical hemolytic uremic syndrome.


RESULTS
Mutations in complement factor H were the first to be associated with atypical hemolytic uremic syndrome. These mutations cluster in the C-terminus of complement factor H. This year has seen the publication of a transgenic mouse model lacking the C-terminus of complement factor H, which spontaneously develops atypical hemolytic uremic syndrome. This mouse model regulated C3 activation in plasma but failed to bind to endothelial cells in an analogous manner to the mutations seen in atypical hemolytic uremic syndrome patients. This year has also seen the emergence of genotype-phenotype correlations in atypical hemolytic uremic syndrome. Patients with membrane cofactor protein mutations have a good prognosis and in those who do develop endstage renal disease, recurrence after transplantation is rare. By contrast, the outcome for patients with complement factor H and complement factor I mutations is poor and the rate of recurrence after transplantation is high. New complement genes associated with atypical hemolytic uremic syndrome have also been described in the past year including factor B, C3, C4b-binding protein, FHR1 and FHR3.


CONCLUSIONS
Genetic screening is now providing prognostically significant information in predicting survival, renal recovery and transplant outcome. It paves the way for the use of complement inhibitors in the future.
Kavanagh
David
D
Renal Division, Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
Goodship
Timothy H
TH
D003165:Complement System Proteins / Q000235:genetics*; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D006801:Humans; D009154:Mutation; D011379:Prognosis
D003165:Complement System Proteins