Complement factor H and hemolytic uremic syndrome. Export

@article{citeulike:2416501, 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.}, address = {Department of Infection Biology, Hans Knoell Institute for Natural Products Research, Beutenbergstr. I1a, 07745 Jena, Germany. zipfel@pmail.hki-jena.de}, author = {Zipfel, P. F. and Skerka, C. and Caprioli, J. and Manuelian, T. and Neumann, H. H. and Noris, M. and Remuzzi, G.}, citeulike-article-id = {2416501}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11367530}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11367530}, issn = {1567-5769}, journal = {Int Immunopharmacol}, keywords = {factor-h}, month = {March}, number = {3}, pages = {461--468}, posted-at = {2008-02-23 02:31:57}, priority = {1}, title = {Complement factor H and hemolytic uremic syndrome.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11367530}, volume = {1}, year = {2001} }

TY - JOUR ID - citeulike:2416501 L3 - citeulike-article-id:2416501 N2 - 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. IS - 3 JF - Int Immunopharmacol SN - 1567-5769 AD - Department of Infection Biology, Hans Knoell Institute for Natural Products Research, Beutenbergstr. I1a, 07745 Jena, Germany. zipfel@pmail.hki-jena.de EP - 468 TI - Complement factor H and hemolytic uremic syndrome. VL - 1 SP - 461 KW - factor-h AU - Zipfel, PF AU - Skerka, C AU - Caprioli, J AU - Manuelian, T AU - Neumann, HH AU - Noris, M AU - Remuzzi, G PY - 2001/03// UR - http://view.ncbi.nlm.nih.gov/pubmed/11367530 ER -