VASCULAR BIOLOGY Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome
نویسندگان
چکیده
Lubka T. Roumenina,1-3 Mathieu Jablonski,1-3 Christophe Hue,1-3 Jacques Blouin,4 Jordan D. Dimitrov,1-3 Marie-Agnes Dragon-Durey,1-4 Mathieu Cayla,1-3 Wolf H. Fridman,1-4 Marie-Alice Macher,5 David Ribes,6 Luc Moulonguet,7 Lionel Rostaing,6 Simon C. Satchell,8 Peter W. Mathieson,8 Catherine Sautes-Fridman,1-3 Chantal Loirat,5 Catherine H. Regnier,1-3 Lise Halbwachs-Mecarelli,9 and Veronique Fremeaux-Bacchi1-4
منابع مشابه
Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome.
Complement is a major innate immune defense against pathogens, tightly regulated to prevent host tissue damage. Atypical hemolytic uremic syndrome (aHUS) is characterized by endothelial damage leading to renal failure and is highly associated with abnormal alternative pathway regulation. We characterized the functional consequences of 2 aHUS-associated mutations (D(254)G and K(325)N) in factor ...
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Atypical hemolytic uremic syndrome (aHUS) is characterized by genetic and acquired abnormalities of the complement system leading to alternative pathway (AP) overactivation and by glomerular endothelial damage, thrombosis, and mechanical hemolysis. Mutations per se are not sufficient to induce aHUS, and nonspecific primary triggers are required for disease manifestation. We investigated whether...
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The complement system is essential for host defense, but uncontrolled complement system activation leads to severe, mostly renal pathologies, such as atypical hemolytic uremic syndrome or C3 glomerulopathy. Here, we investigated a novel combinational approach to modulate complement activation by targeting C3 and the terminal pathway simultaneously. The synthetic fusion protein MFHR1 links the r...
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Atypical hemolytic uremic syndrome (aHUS) is a rare renal thrombotic microangiopathy commonly associated with rare genetic variants in complement system genes, unique to each patient/family. Here, we report 14 sporadic aHUS patients carrying the same mutation, R139W, in the complement C3 gene. The clinical presentation was with a rapid progression to end-stage renal disease (6 of 14) and an unu...
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Atypical hemolytic uremic syndrome (aHUS) may be associated with mutations in the C-terminal of factor H (FH). FH binds to platelets via the C-terminal as previously shown using a construct consisting of short consensus repeats (SCRs) 15 to 20. A total of 4 FH mutations, in SCR15 (C870R) and SCR20 (V1168E, E1198K, and E1198Stop) in patients with aHUS, were studied regarding their ability to all...
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