Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome
| العنوان: | Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome |
|---|---|
| المؤلفون: | Cynthia Abarrategui Garrido, Jorge Esparza-Gordillo, Santiago Rodríguez de Córdoba, Pilar Sánchez-Corral, Elena Arranz, Claire L. Harris, Elena Goicoechea de Jorge, B. Paul Morgan, Luis Carreras, Margarita López-Trascasa |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname ResearcherID |
| بيانات النشر: | National Academy of Sciences (U.S.), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Complement Pathway, Alternative, Complement, Biology, urologic and male genital diseases, medicine.disease_cause, Complement factor B, Pathogenesis, Renal disease, Structure-Activity Relationship, hemic and lymphatic diseases, Atypical hemolytic uremic syndrome, medicine, Humans, Gene, Mutation, Multidisciplinary, CD55 Antigens, Haemolytic uremic syndrome, Biological Sciences, medicine.disease, Complement system, Complement Factor H, Factor H, Hemolytic-Uremic Syndrome, Immunology, Alternative complement pathway, Complement Factor B |
| الوصف: | 31 p.-5 fig.-2 tab. Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in children. Mutations in one or more genes encoding complement-regulatory proteins have been reported in approximately one-third of nondiarrheal, atypical HUS (aHUS) patients, suggesting a defect in the protection of cell surfaces against complement activation in susceptible individuals. Here, we identified a subgroup of aHUS patients showing persistent activation of the complement alternative pathway and found within this subgroup two families with mutations in the gene encoding factor B (BF), a zymogen that carries the catalytic site of the complement alternative pathway convertase (C3bBb). Functional analyses demonstrated that F286L and K323E aHUS-associated BF mutations are gain-of-function mutations that result in enhanced formation of the C3bBb convertase or increased resistance to inactivation by complement regulators. These data expand our understanding of the genetic factors conferring predisposition to aHUS, demonstrate the critical role of the alternative complement pathway in the pathogenesis of aHUS, and provide support for the use of complement-inhibition therapies to prevent or reduce tissue damage caused by dysregulated complement activation This work was supported by Spanish Ministerio de Educación y Cultura Grant SAF2005-00913; Spanish Fondo de Investigaciones Sanitarias Grants G03/054, G03/011, FIS 03/0621, and FIS 01/A046; and Wellcome Trust Grants 068823/Z and 068599. J.E.-G. was supported by European Molecular Biology Organization Long-Term Fellowship LTF 522-2006 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e765ff0ed6a17d280bf071ca00bebc48Test http://hdl.handle.net/10261/67584Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e765ff0ed6a17d280bf071ca00bebc48 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |