Complement factor H and hemolytic uremic syndrome

Peter F. Zipfel, Christine Skerka, Jessica Caprioli, Tamara Manuelian, Hartmut H. Neumann, Marina Noris, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

Factor H is a 150 kDa single chain plasma glycoprotein that plays a pivotal role in the regulation of the alternative pathway of complement. Primary sequence analysis reveals a structural organization of this plasma protein, in 20 homologous units, called Short Consensus Repeats (SCRs), each about 60 amino acids long. Biochemical and genetic studies show an association between factor H deficiency and human diseases, including Systemic Lupus Erythematosus, susceptibility to pyogenic infection and a form of menbranoproliferative glomerulonephropathy. More recently, factor H deficiency has also been associated with susceptibility to Hemolytic Uremic Syndrome (HUS), a disease consisting of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure, caused by platelet thrombi which mainly, but not exclusively, form in the microcirculation of the kidney. In this review, we summarize recent genetic and biochemical data, which indicate a critical role for factor H in the pathogenesis of HUS and suggest an important role of the most C-terminal domain, i.e. SCR 20, in the disease. In addition, we discuss the physiological consequences of these findings, as novel functional data show a particular essential role of SCR 20 of factor H as the central discriminatory and regulatory site of this multidomain, multifunctional plasma protein.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalInternational Immunopharmacology
Volume1
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • Factor H
  • Hemolytic uremic syndrome
  • Short concensus repeats

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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