Complement dysfunction in hemolytic uremic syndrome.
OBJECTIVE
Hemolytic uremic syndrome is a rare disease of microangiopathic hemolytic anemia, low platelet count and is associated with renal impairment. The atypical form, which occurs in adult patients, is associated with defective complement control.


RESULTS
Recent data show that atypical hemolytic uremic syndrome is a genetic disease and gene mutations have been reported for factor H, membrane cofactor protein/CD46 and factor I. All corresponding gene products act in concert and control the activity of the complement convertase C3bBb. This enzyme initiates the alternative pathway as well as amplification of the complement system. Similar to genetic defects, autoantibodies which bind to factor H have been linked to the disease. Defective complement control resulting in hemolytic uremic syndrome explains the disease mechanism and allows improved diagnosis and therapy.


CONCLUSIONS
The atypical form of hemolytic uremic syndrome is associated with defective complement control and inappropriate protein function and may influence disease progression and provide new ways for treatment. Positive effects were reported upon substitution of a defective protein by plasma exchange or plasmaphoreses. The disease recurrence rate for renal transplants depends on the type of gene mutated; patients with mutations in the membrane cofactor protein gene have a better prognosis than patients with mutations in other genes.
Zipfel
Peter F
PF
Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstrasse 11a, D-07743 Jena, Germany. peter.zipfel@hki-jena.de
Skerka
Christine
C
D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000235:genetics; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000628:therapy; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics; D009154:Mutation; D010956:Plasmapheresis / Q000379:methods; D010976:Platelet Count; D011379:Prognosis
D001323:Autoantibodies; D003165:Complement System Proteins