A5078916747- Monoclonal and Polyclonal Antibodies Research
- Kawasaki Disease and Coronary Complications
- Complement system in diseases
- Blood groups and transfusion
- Erythrocyte Function and Pathophysiology
- Platelet Disorders and Treatments
- Glycosylation and Glycoproteins Research
- Blood disorders and treatments
- Cell Adhesion Molecules Research
- Coronary Artery Anomalies
- Phagocytosis and Immune Regulation
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Pneumonia and Respiratory Infections
- Hemoglobinopathies and Related Disorders
- Blood Coagulation and Thrombosis Mechanisms
- Autoimmune and Inflammatory Disorders Research
- Peptidase Inhibition and Analysis
- Hemophilia Treatment and Research
- Chronic Lymphocytic Leukemia Research
- Emergency and Acute Care Studies
- Immune Cell Function and Interaction
- Respiratory viral infections research
University of Amsterdam
2014-2025
Sanquin
2014-2025
Amsterdam University Medical Centers
2019-2025
University Children's Hospital Zurich
2022-2023
University of Zurich
2022-2023
Emma Kinderziekenhuis
2003-2023
Imperial College London
2022-2023
Radboud University Nijmegen
2023
Radboud University Medical Center
2023
Radboud Institute for Molecular Life Sciences
2023
Human Fcgamma receptors (FcgammaRs) are glycoproteins that bind the Fc region of IgG. The genes encoding low-affinity FcgammaRs located on chromosome 1q23-24. Beside single nucleotide polymorphisms (SNPs), gene copy number variation (CNV) is now being recognized as an important indicator for inter-individual differences. Recent studies identifying CNV in human genome suggest large areas at 1q23-24 to be involved, and this has been associated with manifestations systemic autoimmune disease....
The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, not clear. Unlike other Fcγ receptors (FcγR), it a glycophosphatidyl inositol (GPI) -anchored molecule does have intracellular signaling motifs. Nevertheless, can cooperate with FcγR to promote phagocytosis antibody-opsonized microbes by neutrophils. Here we investigated role during antibody-dependent cellular cytotoxicity (ADCC) neutrophils towards solid cancer...
Abstract The balance between activating and inhibitory signals from the different FcγRs for IgG ensures homeostasis of many inflammatory responses. FCGR2C is product an unequal crossover FCGR2A FCGR2B genes encoding FcγRIIa (CD32a) FcγRIIb (CD32b), respectively. A single nucleotide polymorphism (SNP) in exon 3 results either expression FcγRIIc (CD32c) (FCGR2C-open reading frame [ORF]) or its absence because a stop codon (FCGR2C-Stop). Two additional variations FcγRIIb/c on leukocytes have...
To determine relevant Fc-gamma receptor (FcγR) polymorphisms in relation to susceptibility SLE and LN, the functional consequences of genetic associations found.Using multiplex ligation-dependent probe amplification, copy number regions (CNRs) known single nucleotide FcγRII FcγRIII were determined a LN-enriched cohort 266 Dutch Caucasian patients 919 healthy controls. Expression FcγRs on leukocytes was assessed using flow cytometry.In multivariable analysis, low CNR1 (including FCGR3B; odds...
The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All low-affinity FcγRs are encoded the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) gene copy number variants. This is notoriously difficult to genotype high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at in >4,000 individuals define linkage...
Abstract Neutrophils are particularly well known for their antimicrobial function. Although historically they regarded as strictly a phagocyte of the innate immune system, over time it has become clear that neutrophils versatile cells with numerous functions including and adaptive regulation. We have previously described role human in antibody-mediated red blood cell (RBC) clearance. Under homeostatic conditions, do not take up RBCs. Yet, when RBCs immunoglobulin G (IgG) opsonized, which can...
To examine the possible use of magnetocardiography in diagnosis fetal arrhythmias.Investigation routinely examined pregnant women, as well women referred because arrhythmias or other reasons.Sixty-three between 13th and 42nd week pregnancy.Recording 189 magnetocardiograms, which 173 traces (92%) demonstrated sufficient signal strength to permit evaluation. After digital subtraction maternal artefact, all complexes were identified recording was for arrhythmic events.Short bradycardic...
An infectious agent was isolated from leg tendons of broiler breeders with clinical tenosynovitis. The grew well on the chorioallantoic membrane (CAM) embryonating chicken eggs and filterable through a 0.22-Ft filter. Typical gross microscopic lesions tenosynovitis could be reproduced in chicks via oral, subcutaneous, or intra-abdominal routes, as contact control chicks. Precipitating antibodies against homologous two other avian reoviruses were present beginning 14 days postinoculation....
Retrotransposon-mediated insertion of a long interspersed nuclear element (LINE)-1 or an Alu into human gene is well-known pathogenic mechanism. We report novel LINE-1-mediated transcript from the TMF1 on chromosome 3 CYBB X-chromosome. In Dutch male patient with chronic granulomatous disease, 5.8-kb, incomplete and partly exonized was identified in intron 1 CYBB, opposite orientation to host gene. The sequence showed hallmarks retrotransposition event, antisense poly(A) tail, target site...
The complement factor H-related (FHR) proteins are hypothesized to fine-tune the regulatory role of H (FH) in alternative pathway system. Moreover, FHR-1, FHR-2 and FHR-5 have been proposed be dimers, which further complicates accurate analysis. As FHRs highly similar among themselves towards FH, obtaining specific reagents for quantification serum levels functional analysis is challenging. In this study, we generated antibodies developed ELISAs measure serum. We used both recombinant...
Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in (MIS-C) often present clinical features that resemble Kawasaki disease (KD). Disease severity adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated KD and MIS-C. Therefore, we explored immunological response, correlates both disorders.Eighteen inflammatory plasma protein levels seven were measured (n = 216) MIS-C 56)...
Human neutrophils were found to express all known Toll-like receptors (TLRs) except TLR3 and TLR7. IRAK-4-deficient tested for their responsiveness various TLR ligands. Essentially responses in neutrophils, including the induction of reactive oxygen species generation, adhesion, chemotaxis IL-8 secretion, be dependent on IRAK-4. Surprisingly, reactivity towards certain established ligands, imiquimod ODN-CpG, was unaffected by IRAK-4 deficiency, demonstrating activity is independent TLR....
The major human complement regulator in blood, factor H (FH), has several closely related proteins, called FH-related (FHR) proteins. As all FHRs lack relevant regulatory activity, their physiological role is not well understood. FHR protein 3 (FHR-3) been suggested to compete with FH for binding Neisseria meningitidis, thereby affecting complement-mediated clearance. Clearly, the vivo outcome of such competition greatly depends on and FHR-3 concentrations. While levels have established,...
The efficacy of cancer therapeutic antibodies varies considerably among patients. Anti-cancer act through different mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) triggered via Fcγ receptors (FcγR). This phagocyte ADCC can be promoted by interference with CD47-SIRPα interactions, but the magnitude this enhancement also individuals. Both FcγR and SIRPα display considerable genetic variation, we investigated whether explains some variability in ADCC. Because linkage...
Abstract Objective To investigate whether common genetic variants in the vascular endothelial growth factor (VEGF) gene are associated with Kawasaki disease (KD) and subsequent development of coronary artery lesions. Methods Common VEGF were analyzed an association study a Dutch cohort 170 KD patients 300 healthy Caucasian controls. Genotyping was done 5′‐nuclease TaqMan assays 3′‐hybridization–triggered fluorescence minor groove binder Eclipse assays. Results An susceptibility to observed 2...
Summary Kawasaki disease (KD) is an acute vasculitis occurring in young children. Its aetiology unknown, but infectious agent assumed. Increased levels of proinflammatory cytokines and chemokines have been reported KD. Genetic variation these genes the receptors for could influence regulation chemokines. In a case–control study 170 Dutch Caucasian KD patients 300 healthy controls, common genetic variants chemokine receptor CCR3, CCR2, CCR5, CX3CR1, CXCR1 CXCR2 were analysed. Of eight studied...