Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome

Kidney Int. 2006 Mar;69(6):981-8. doi: 10.1038/


We investigated the phenotypic expression of factor H mutations in two patients with atypical hemolytic uremic syndrome (HUS). Factor H in serum was assayed by rocket immunoelectrophoresis, immunoblotting, and double immunodiffusion and in tissue by immunohistochemistry. Functional activity was analyzed by hemolysis of sheep erythrocytes and binding to endothelial cells. A homozygous mutation in complement control protein (CCP) domain 10 of factor H was identified in an adult man who first developed membranoproliferative glomerulonephritis and later HUS. C3 levels were very low. The patient had undetectable factor H levels in serum and a weak factor H 150 kDa band. Double immunodiffusion showed partial antigenic identity with factor H in normal serum owing to the presence of factor H-like protein 1. Strong specific labeling for factor H was detected in glomerular endothelium, mesangium and in glomerular and tubular epithelium as well as in bone marrow cells. A heterozygous mutation in CCP 20 of factor H was found in a girl with HUS. C3 levels were moderately decreased at onset. Factor H levels were normal and a normal 150 kDa band was present. Double immunodiffusion showed antigenic identity with normal factor H. Factor H labeling was minimal in the renal cortex. Factor H dysfunction was demonstrated by increased sheep erythrocyte hemolysis and decreased binding to endothelial cells. In summary, two different factor H mutations associated with HUS were examined: in one, factor H accumulated in cells, and in the other, membrane binding was reduced.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / chemistry
  • Child
  • Complement C3 / analysis
  • Complement Factor H / analysis
  • Complement Factor H / genetics*
  • Complement Factor H / physiology
  • Endothelium / chemistry
  • Endothelium / pathology
  • Endothelium / physiopathology
  • Erythrocytes / pathology
  • Female
  • Flow Cytometry
  • Gene Expression
  • Glomerulonephritis, Membranoproliferative / complications
  • Glomerulonephritis, Membranoproliferative / genetics
  • Hemolysis / genetics
  • Hemolysis / physiology
  • Hemolytic-Uremic Syndrome / blood
  • Hemolytic-Uremic Syndrome / etiology
  • Hemolytic-Uremic Syndrome / genetics*
  • Humans
  • Immunodiffusion
  • Immunoelectrophoresis
  • Immunohistochemistry
  • Kidney Cortex / chemistry
  • Male
  • Mesangial Cells / chemistry
  • Middle Aged
  • Mutation*
  • Phenotype*
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein Structure, Tertiary / genetics
  • Sheep


  • Complement C3
  • Complement Factor H