A5016484576- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Blood groups and transfusion
- Erythrocyte Function and Pathophysiology
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Monoclonal and Polyclonal Antibodies Research
- Blood Coagulation and Thrombosis Mechanisms
- Platelet Disorders and Treatments
- Adenosine and Purinergic Signaling
- Glycosylation and Glycoproteins Research
- Retinal Diseases and Treatments
- Neonatal Health and Biochemistry
- Renal Transplantation Outcomes and Treatments
- Vitamin K Research Studies
- Blood properties and coagulation
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Neuroscience of respiration and sleep
- Pregnancy and preeclampsia studies
- Neonatal and Maternal Infections
- Drug Transport and Resistance Mechanisms
- Streptococcal Infections and Treatments
- Immune Cell Function and Interaction
- Connective tissue disorders research
Centre for Biomedical Network Research on Rare Diseases
2013-2023
Hospital La Paz Institute for Health Research
2011-2023
Hospital Universitario La Paz
2011-2022
Instituto de Investigación de Enfermedades Raras
2011-2022
Centro de Investigación Biomédica en Red
2009-2018
Centro de Investigaciones Biológicas Margarita Salas
1991-2017
Hospital Universitario Virgen del Rocío
2007
Consejo Superior de Investigaciones Científicas
2000-2002
Hospital Universitario Fundación Jiménez Díaz
1986-2000
Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in children. Mutations one or more genes encoding complement-regulatory proteins have been reported approximately one-third nondiarrheal, atypical HUS (aHUS) patients, suggesting a defect the protection cell surfaces against complement activation susceptible individuals. Here, we identified subgroup aHUS patients showing persistent alternative pathway and found within this two families with mutations gene factor B...
Several abnormalities in complement genes reportedly contribute to atypical hemolytic uremic syndrome (aHUS), but incomplete penetrance suggests that additional factors are necessary for the disease manifest. Here, we sought describe genotype–phenotype correlations among patients with combined mutations, defined as mutations more than one gene. We screened 795 aHUS and identified single 41% 3%. Only 8%–10% of CFH, C3, or CFB had whereas approximately 25% MCP CFI mutations. The concomitant...
The efficiency of the complement system as an innate immune defense mechanism depends on a fine control that restricts its action to pathogens and prevents non-specific damage host tissues. Genetic functional analyses have shown this critical activation may be impaired in atypical hemolytic uremic syndrome (aHUS) patients. Mutations HF1 , MCP or FI been found aHUS patients, but incomplete penetrance disease individuals carrying these mutations is relatively frequent no genetic defect has yet...
C3 glomerulopathies (C3G) are a group of severe renal diseases with distinct patterns glomerular inflammation and deposition caused by complement dysregulation. Here we report the identification familial C3G-associated genomic mutation in gene factor H–related 1 (CFHR1), which encodes FHR1. The resulted duplication N-terminal short consensus repeats (SCRs) that conserved FHR2 FHR5. We determined native FHR1, FHR2, FHR5 circulate plasma as homo- hetero-oligomeric complexes, formation is...
Atypical hemolytic uremic syndrome (aHUS) is a disease of anemia, thrombocytopenia, and renal failure associated with defective alternative pathway (AP) complement control. Previously, we presented database (www.FH-HUS.org) focusing on aHUS mutations in the Factor H gene (CFH). Here, new are reported for regulatory proteins (FH), I (FI), membrane cofactor protein (MCP). Additional or polymorphisms within CFH have been membranoproliferative glomerulonephritis (MPGN) age-related macular...
Many of the complement regulatory genes within RCA cluster (1q32) have arisen through genomic duplication and resulting high degree sequence identity is likely to predispose gene conversion events. The highest between for factor H (CFH) five H-related proteins--CFHL1, CFHL2, CFHL3, CFHL4, CFHL5. CFH mutations are associated with atypical hemolytic uremic syndrome (aHUS). In Newcastle cohort 157 aHUS patients we identified in 25 families or individuals. Eleven these independent either...
Abstract Complement is an essential humoral component of innate immunity; however, its inappropriate activation leads to pathology. Polymorphisms, mutations, and autoantibodies affecting factor H (FH), a major regulator the alternative complement pathway, are associated with various diseases, including age-related macular degeneration, atypical hemolytic uremic syndrome, C3 glomerulopathies. Restoring FH function could be treatment option for such pathologies. In this article, we report on...
Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused complement dysregulation. Consistently, inhibition therapies are highly effective in most patients with atypical syndrome. Recently, it was shown that a significant percentage of early-onset carry mutations diacylglycerol kinase-ε, an intracellular protein no obvious role complement. These data support alternative, complement-independent mechanism leading to thrombotic microangiopathy has implications...
Abstract Atypical hemolytic uremic syndrome (aHUS) is a renal disease associated with complement alternative pathway dysregulation and characterized by endothelial injury. Pentraxin 3 (PTX3) soluble pattern recognition molecule expressed cells upregulated under inflammatory conditions. PTX3 activates complement, but it also binds the inhibitor factor H. In this study, we show that native H, H-like protein 1, H-related 1 (CFHR1) bind to PTX3-bound H maintain their regulatory activities. PTX3,...
Atypical hemolytic uremic syndrome (aHUS) associates with complement dysregulation caused by mutations and polymorphisms in activators regulators. However, the reasons why some proteins predispose to aHUS are poorly understood. Here, we have investigated functional consequences of three aHUS-associated C3, R592W, R161W I1157T. First, provide evidence that penetrance disease severity for these is modulated inheritance documented "risk" haplotypes as has been observed other genes. Next, show...
Significance Statement Mutations in factor H–related protein 1 (FHR-1) that result duplication of its dimerization domain associate with the chronic renal disease C3 glomerulopathy (C3G), which is characterized by complement dysregulation. The molecular basis for this association only partially understood. authors show these FHR-1 mutations enhance FHR-1’s binding to C3-activated fragments on opsonized surfaces and promote an excessive activation overcomes FH regulation. They also elevated...
Abstract A key step in the elimination of invading pathogens from body is covalent binding complement proteins C3b and C4b to their surface. However, many have evolved mechanisms avoid system host. Understanding how these work may lead more efficacious forms therapy. Here we provide an insight into molecular basis Streptococcus pyogenes binds human plasma C4b-binding protein (hC4BP), a regulatory molecule that decrease deposition on streptococcal We show surface molecules bind site hC4BP...