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

Fariba Vaziri-Sani, L Holmberg, A G Sjöholm, A C Kristoffersson, M Manea, V Fremeaux-Bacchi, I Fehrman-Ekholm, R Raafat, D Karpman

Forskningsoutput: TidskriftsbidragArtikelPeer review

81 Citeringar (Scopus)

Sammanfattning

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.

OriginalspråkEngelska
Sidor (från-till)981-988
Antal sidor7
TidskriftKidney International
Volym69
Utgåva6
DOI
StatusPublicerad - 2006
Externt publiceradJa

Nationell ämneskategori

  • Cell- och molekylärbiologi (30108)
  • Immunologi inom det medicinska området (30110)

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