A5008114290- Complement system in diseases
- Blood groups and transfusion
- Renal Diseases and Glomerulopathies
- Monoclonal and Polyclonal Antibodies Research
- Erythrocyte Function and Pathophysiology
- Mosquito-borne diseases and control
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Retinal Diseases and Treatments
- Systemic Lupus Erythematosus Research
- Hemoglobinopathies and Related Disorders
- Virology and Viral Diseases
- Platelet Disorders and Treatments
- T-cell and B-cell Immunology
- Blood Coagulation and Thrombosis Mechanisms
- Pregnancy and preeclampsia studies
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Malaria Research and Control
- Glycosylation and Glycoproteins Research
- Reproductive System and Pregnancy
- Virus-based gene therapy research
- Adenosine and Purinergic Signaling
- Labor market dynamics and wage inequality
- SARS-CoV-2 and COVID-19 Research
Washington University in St. Louis
2016-2025
University of Helsinki
2017-2024
Atkins (United States)
2023
Canadian Cancer Society
2017-2020
Center for Rheumatology
1991-2019
MSD (Norway)
2017-2019
Helsinki University Hospital
2017
Institute for Molecular Medicine Finland
2017
Mayo Clinic
2017
University of British Columbia
2016
Hereditary angioedema is manifested by attacks of swelling the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously secondary to trauma. It inherited as an autosomal dominant trait and due deficient activity inhibitor activated first component complement. The clinical diagnosis can be confirmed findings low levels C4 C1 esterase activity, both. Therapy may divided into three phases: long-term prophylaxis attacks, short-term treatment acute attacks. Long-term...
Membrane cofactor protein (MCP; CD46) is a widely expressed transmembrane complement regulator. Like factor H it inhibits activation by regulating C3b deposition on targets. Factor mutations occur in 10–20% of patients with hemolytic uremic syndrome (HUS). We hypothesized that MCP could predispose to HUS, and we sequenced coding exons affected individuals from 30 families. were detected three families: deletion two amino acids (D237/S238) family 1 (heterozygous) substitution, S206P, families...
Based on preliminary evidence indicating that a cell-associated protein of U937 (a human monocyte-like cell line) possessed cofactor activity and was not the C3b/C4b receptor, we sought to further characterize this protein. A sequential four-column purification procedure devised includes C3(H2O) affinity chromatography isolate in reasonable yields purity several other lines. its pattern Mr SDS-PAGE, acidic pI, ligand specificity, it is identical recently described or C3b-binding membrane...
Purpose.: Several genes encoding complement system components and fragments are associated with age-related macular degeneration (AMD). This study was conducted to determine whether alterations in circulating levels of these markers activation regulation also independently advanced AMD they related genotypes. Methods.: Plasma DNA samples were selected from individuals our registry who had progressed or developed the stages AMD, including 58 geographic atrophy 62 neovascular disease. Subjects...
Jane Salmon and colleagues studied 250 pregnant patients with SLE and/or antiphospholipid antibodies found an association of risk variants in complement regulatory proteins who developed preeclampsia, as well preeclampsia lacking autoimmune disease.
Pili of Neisseria gonorrhoeae and meningitidis mediate binding the bacteria to human cell‐surface receptors. We found that purified pili bound a 55‐ 60‐kDa doublet band on SDS–PAGE separated epithelial cell extracts. This is migration pattern typical membrane cofactor protein (MCP or CD46). MCP widely distributed complement regulatory protein. Attachment cells was blocked by polyclonal monoclonal antibodies directed against MCP, suggesting this regulator receptor for piliated . proved...
ABSTRACT The 51 human adenovirus serotypes are divided into six species (A to F). Many adenoviruses use the coxsackie-adenovirus receptor (CAR) for attachment host cells in vitro. Species B do not compete with CAR-binding binding cells, and it has been suggested that a other than CAR. mainly cause disease respiratory tract, eyes, urinary tract. Here we demonstrate type 11 (Ad11; of B) binds Chinese hamster ovary (CHO) transfected CD46 (membrane cofactor protein)-cDNA at least 10 times more...
Abstract Complement promotes the rapid recognition and elimination of pathogens, infected cells, immune complexes. The biochemical basis for its target specificity is incompletely understood. In this report, we demonstrate that properdin can directly bind to microbial targets provide a platform in situ assembly function alternative pathway C3 convertases. This mechanism differs from standard model wherein nascent C3b generated fluid phase attaches nonspecifically targets. Properdin-directed...
cDNAs encoding the complement decay-accelerating factor (DAF) were isolated from HeLa and differentiated HL-60 lambda gt cDNA libraries by screening with a codon preference oligonucleotide corresponding to DAF NH2-terminal amino acids 3-14. The composite sequence showed 347-amino acid protein preceded an leader peptide sequence. translated beginning at NH2 terminus encodes four contiguous approximately equal 61-amino long repetitive units of internal homology. regions contain conserved...
Dengue virus (DENV) nonstructural protein-1 (NS1) is a secreted glycoprotein that absent from viral particles but accumulates in the supernatant and on plasma membrane of cells during infection. Immune recognition cell surface NS1 endothelial has been hypothesized as mechanism for vascular leakage occurs severe DENV However, it remained unclear how becomes associated with membrane, contains no membrane-spanning sequence motif. Using flow cytometric ELISA-based binding assays mutant lines...
The complement system, by virtue of its dual effector and priming functions, is a major host defense against pathogens. Flavivirus nonstructural protein (NS)-1 has been speculated to have immune evasion activity, because it secreted glycoprotein, binds back cell surfaces, accumulates high levels in the serum infected patients. Herein, we demonstrate an immunomodulatory function West Nile virus NS1. Soluble cell-surface-associated NS1 recruits regulatory factor H, resulting decreased...
Variants in the complement factor H gene (CFH) are associated with age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5) lie within regulators of activation (RCA) locus on chromosome 1q32. Aims Methods. In this study, structural evolutionary relationships between these AMD was refined using a combined genetic, molecular immunohistochemical approach.We identify characterize large, common deletion that encompasses both CFHR1 CFHR3 genes. CFHR1, an abundant serum...
Hemolytic uremic syndrome (HUS) is characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. The non–Shiga toxin–associated HUS (atypical [aHUS]) has been shown to be a disease complement dysregulation. Mutations in plasma regulators factor H I widely expressed membrane cofactor protein (MCP; CD46) have described recently. This study looked for MCP mutations panel 120 patients with aHUS. In this cohort, approximately 10% aHUS (11 patients;...