Navegando por Palavras-chave "complement system"

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    Association of complement factor H Y402H polymorphism and age-related macular degeneration in Brazilian patients
    (Wiley-Blackwell, 2010-08-01) Teixeira, Anderson G. [UNIFESP]; Silva, Aldacilene S.; Lin, Fabio L. H.; Velletri, Roberta [UNIFESP]; Bavia, Lorena; Belfort, Rubens Junior [UNIFESP]; Isaac, Lourdes; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Purpose:The aim of this study was investigate the association between complement Factor H polymorphism (Y402H) and age-related macular degeneration (AMD) in Brazilian patients.Methods:Patients with AMD aged 50 or more and age-matched healthy controls were enrolled in the study. Genomic DNA was isolated from leucocytes of patients and controls; the Y402H polymorphism of complement Factor H gene (CFH) was determined by polymerase chain reaction directed sequencing.Results:The frequency of 1277C allele of Factor H was 56.30% in patients with AMD compared with 36.51% in controls (p-value = 0.001). the genotypic distribution differed significantly between the two groups (1277CC 36.98%, 1277CT 38.65% and 1277TT 24.37% for AMD group; 1277CC 13.16%, 1277CT 46.71% and 1277TT 40.13% for controls, p-value = 0.001). the odds ratio for patients with AMD carrying only one 1277C allele was 1.36 and for those carrying two 1277C alleles was 4.63, when compared to the control group.Conclusions:These results suggest the Y402H polymorphism of CFH is a risk factor to the development of AMD in Brazilian patients. This is in accordance with findings from the majority of previous study population in Europe and North American.
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    Vitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis
    (Federation Amer Soc Exp Biol, 2011-10-01) Mesnard, Laurent; Rafat, Cedric; Vandermeersch, Sophie; Hertig, Alexandre; Cathelin, Dominique; Xu-Dubois, Yi-Chun; Jouanneau, Chantal; Keller, Alexandre Castro [UNIFESP]; Ribeil, Jean-Antoine; Leite-de-Moraes, Maria C.; Rondeau, Eric; Univ Paris 06; Hop Necker Enfants Malad; Universidade Federal de São Paulo (UNIFESP)
    During human glomerulonephritis, the severity of injuries correlates with glomerular fibrin deposits, which are tightly regulated by the intraglomerular fibrinolytic system. Here, we evaluated the role of vitronectin (VTN; also known as complement S protein), the principal cofactor of the plasminogen activator inhibitor-1 (PAI-1), in a mouse model of acute glomerulonephritis. We found that in mice subjected to nephrotoxic serum, the absence of VTN resulted in a lower glomerular PAI-1 activity and a higher glomerular fibrinolytic activity. Challenged VTN-/- mice displayed significantly less fibrin deposits, proteinuria, and renal failure than their wild-type counterparts. Notably, this protective effect afforded by VTN deficiency was still observed after a C3 depletion. Finally, the injection of VTN+/+ serum in VTN-/- mice induced the glomerular deposition of VTN, increased PAI-1 deposition, decreased glomerular fibrinolytic activity, and aggravated glomerular injury. As in mice, abundant glomerular VTN deposits were also observed in patients with severe glomerulonephritis. Here, we show that plasma-exchange therapy, admittedly beneficial in this clinical context, induces a significant depletion in circulating VTN, which might modulate PAI-1 activity locally and accelerate the clearance of fibrin deposits in the glomeruli. Collectively, these results demonstrate that VTN exerts a deleterious role independently from complement, by directing PAI-dependent fibrinolysis in the glomerular compartment.-Mesnard, L., Rafat, C., Vandermeersch, S., Hertig, A., Cathelina, D., Xu-Dubois, Y. -C., Jouanneau, C., Castro Keller, A., Ribeil, J. -A., Leite-de-Moraes, M. C., Rondeau, E. Vitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis. FASEB J. 25, 3543-3553 (2011). www.fasebj.org