Alternative complement pathway assessment in patients with atypical HUS

The atypical Hemolytic Uremic Syndrome (aHUS) is a rare thrombotic microangiopathy leading to end stage renal disease in approximately 60% of patients. Over the last decade, a clear link has been demonstrated between this disease and defective complement regulation. The hallmark of the aHUS is the a...

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Veröffentlicht in:	Journal of immunological methods Jg. 365; H. 1-2; S. 8 - 26
Hauptverfasser:	Roumenina, Lubka T., Loirat, Chantal, Dragon-Durey, Marie-Agnes, Halbwachs-Mecarelli, Lise, Sautes-Fridman, Catherine, Fremeaux-Bacchi, Veronique
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Amsterdam Elsevier B.V 28.02.2011 Elsevier
Schlagworte:	antibodies Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized Atypical Hemolytic Uremic Syndrome Biological and medical sciences C3 convertase Complement Complement blockers Complement C3 - chemistry Complement C3 - genetics Complement C3 - metabolism Complement C3 Convertase, Alternative Pathway - biosynthesis Complement C3 Convertase, Alternative Pathway - chemistry Complement C3 Convertase, Alternative Pathway - genetics Complement Factor B - chemistry Complement Factor B - genetics Complement Factor B - metabolism Complement Factor H - chemistry Complement Factor H - genetics Complement Factor H - metabolism Complement Inactivating Agents - therapeutic use Complement Pathway, Alternative - genetics Complement System Proteins - chemistry Complement System Proteins - genetics Complement System Proteins - metabolism Defective complement regulators Factor H Fundamental and applied biological sciences. Psychology Fundamental immunology genes genetic disorders Genetic Techniques genetic techniques and protocols hemolytic uremic syndrome Hemolytic-Uremic Syndrome - diagnosis Hemolytic-Uremic Syndrome - genetics Hemolytic-Uremic Syndrome - immunology Hemolytic-Uremic Syndrome - therapy Humans Immunologic Tests Kidney Transplantation mechanism of action microangiopathy Models, Molecular Molecular immunology Mutation patients Plasma Exchange protein synthesis screening Techniques therapeutics Complement blockers Defective complement regulators Factor H Complement Atypical Hemolytic Uremic Syndrome C3 convertase Kidney disease Human Thrombocytopenia Urinary system disease Hemolytic uremic syndrome Alternative pathway complement Acute Hemopathy Immunological method Platelet Hemolytic anemia Renal failure
ISSN:	0022-1759, 1872-7905, 1872-7905
Online-Zugang:	Volltext
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Zusammenfassung:	The atypical Hemolytic Uremic Syndrome (aHUS) is a rare thrombotic microangiopathy leading to end stage renal disease in approximately 60% of patients. Over the last decade, a clear link has been demonstrated between this disease and defective complement regulation. The hallmark of the aHUS is the association with mutations in complement alternative pathway genes. Endothelial damage is related to complement dysregulation, but the exact mechanism is just starting to be elucidated. Screening for and characterization of mutations in the components of the C3 convertase (C3 and FB) or its regulators (FH, FI, MCP, and Thrombomodulin) or anti-FH antibodies has become an indispensable part of the disease's diagnostic. This review will initially summarize current knowledge on the understanding of complement activation and regulation, followed by a description on the genetic analysis as well as the methods used for complement protein quantification. Another part of this review will focus on the mechanisms of action of aHUS-associated mutations. We will emphasize on when and why some mutations lead to protein deficiency, while others result in — to dysfunctional but normally expressed proteins. Finally, we will discuss how the therapy of aHUS patients can be modified according to the functional consequences of each particular genetic defect.
Bibliographie:	http://dx.doi.org/10.1016/j.jim.2010.12.020 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Review-3 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0022-1759 1872-7905 1872-7905
DOI:	10.1016/j.jim.2010.12.020