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Complement factor H and hemolytic uremic syndrome.

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 membranoproliferative 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.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zipfel PF,Skerka C,Caprioli J,Manuelian T,Neumann HH,Noris M,Remuzzi G

doi

10.1016/s1567-5769(00)00047-3

keywords:

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

461-8

issue

3

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(00)00047-3

journal_volume

1

pub_type

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