A5049420130- Complement system in diseases
- Blood groups and transfusion
- Renal Diseases and Glomerulopathies
- Vector-borne infectious diseases
- Streptococcal Infections and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Erythrocyte Function and Pathophysiology
- Platelet Disorders and Treatments
- Bacterial Infections and Vaccines
- Adenosine and Purinergic Signaling
- Viral Infections and Vectors
- Neonatal and Maternal Infections
- Mosquito-borne diseases and control
- Cell Adhesion Molecules Research
- Malaria Research and Control
- Glycosylation and Glycoproteins Research
- Antimicrobial Resistance in Staphylococcus
- Hemoglobinopathies and Related Disorders
- Toxin Mechanisms and Immunotoxins
- Hemophilia Treatment and Research
- Liver Disease and Transplantation
- Infective Endocarditis Diagnosis and Management
- Retinal Diseases and Treatments
- Inflammatory Bowel Disease
University of Helsinki
2015-2025
United Medix Laboratories (Finland)
2017-2023
Helsinki University Hospital
2007-2021
University of Chicago
2007
École Polytechnique Fédérale de Lausanne
2007
Arkana Laboratories
2007
Flinders Medical Centre
2000-2003
Flinders University
2000-2002
Bernhard Nocht Institute for Tropical Medicine
1999-2000
University of South Australia
2000
Abstract Complement factor H (FH) is an important regulator of the alternative complement pathway. The Y402H polymorphism within seventh short consensus repeat FH was recently shown to be associated with age-related macular degeneration, most common cause irreversible blindness in Western world. We examined effects this on various functions. purified from sera degeneration patients homozygous for FH402H variant showed a significantly reduced binding C-reactive protein (CRP), acute phase...
The alternative pathway of complement is important in innate immunity, attacking not only microbes but all unprotected biological surfaces through powerful amplification. It unresolved how host and nonhost are distinguished at the molecular level, key components domains 19–20 regulator factor H (FH), which interact with (i.e., nonactivator surface glycosaminoglycans or sialic acids) C3d part C3b. Our structure FH19–20:C3d complex 2.3-Å resolution shows that FH19–20 has two distinct binding...
Pseudomonas aeruginosa is an opportunistic human pathogen that can cause a wide range of clinical symptoms and infections are frequent in immunocompromised patients. In this study, we show P. evades complement attack by binding the plasma regulators Factor H H-related protein-1 (FHR-1) to its surface. binds intact bacteria via two sites located within short consensus repeat (SCR) domains 6-7 19-20, FHR-1 SCR domain 3-5. A protein was isolated using affinity matrix, identified mass...
Abstract C-reactive protein (CRP) is a major acute phase whose functions are not totally clear. In this study, we examined the interaction of CRP with factor H (FH), key regulator alternative pathway (AP) complement. Using surface plasmon resonance technique and panel recombinantly expressed FH constructs, observed that binds to two closely located regions on short consensus repeat (SCR) domains 7 8–11 FH. Also FH-like 1 (FHL-1), an alternatively spliced product gene, bound its most...
Abstract The long pentraxin PTX3 is a multifunctional soluble molecule involved in inflammation and innate immunity. As an acute phase protein, binds to the classical pathway complement protein C1q, limits tissue damage inflammatory conditions by regulating apoptotic cell clearance, plays role phagocytosis of selected pathogens. This study was designed investigate interaction with factor H (FH), main alternative regulatory protein. We report that FH apparent Kd 1.1 × 10−7 M, define two...
Autoantibodies targeting factor H (FH), which is a main alternative complement pathway regulatory protein, have been well characterized in atypical hemolytic uremic syndrome (aHUS) but less described association with pathway-mediated glomerulopathies (GP). In this study, we studied 17 patients presenting GP who were positive for anti-FH IgG. Clinical data collected and biological characteristics compared those of Ab-associated aHUS. contrast to the aHUS patients, had no circulating...
To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm innate immunity, alternative pathway complement. It can attack all kinds targets is tightly controlled in plasma on cells by complement regulator factor H (FH). FH binds simultaneously cell surface structures such as heparin or glycosaminoglycans via domain 20 main opsonin C3b 19. Many pathogenic protect themselves from recruiting FH. We analyzed how why different bind...
ABSTRACT The most characteristic features of the Lyme disease pathogens, Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and circumvent immune defenses host for extended periods time, despite elevated levels borrelia-specific antibodies in serum other body fluids. Our aim present study was determine whether B. is able interfere with complement (C) at level C3 by accelerating C3b inactivation thus inhibit amplification C cascade. Strains belonging different...
Abstract A unique monoclonal Ig λ light chain dimer (protein LOI) was isolated from the serum and urine of a patient with hypocomplementemic membranoproliferative glomerulonephritis. In vitro efficiently activated alternative pathway complement (AP). When added to normal human serum, LOI temporarily enhanced AP hemolytic activity, but during prolonged incubation activity depleted. Protein found bind factor H, main regulator molecule AP. By binding short consensus repeat domain 3 blocked one...
Abstract The complement inhibitor factor H (fH) interacts via its seventh short consensus repeat (SCR) domain with multiple ligands including heparin, streptococcal M protein and C‐reactive (CRP). aim of this study was to localize the residues in SCR 7 required for these interactions. We initially built a homology model fH 6–7 using averaged NMR structures 15–16 vaccinia control 3–4 as templates. Electrostatic potentials model's surface demonstrated co‐localization three clusters positively...
Summary The complement inhibitor Factor H has three distinct binding sites for C3b and heparin, but in solution uses specifically the most C-terminal domain, i.e. short consensus repeats (SCR) 20 ligand interaction. Two novel monoclonal antibodies (mABs C14 C18) that bind to domain SCR completely blocked interaction of with ligands C3b, C3d, heparin endothelial cells. In contrast, several mAbs N-terminus middle regions molecule showed no or minor inhibitory effects when assayed by...
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 a major innate immune surveillance system. One of its most important regulators the plasma protein factor H (FH). FH inactivation by mutations or autoantibodies associated with thrombotic microangiopathy disease, atypical hemolytic uremic syndrome. In this study, we report characterization blood samples from 19 anti-FH Ab-positive syndrome patients collected at acute phase disease. Analyses functional consequences and epitope mapping, using both fluid solid approaches,...