A5026233841- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood disorders and treatments
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Immune responses and vaccinations
- Platelet Disorders and Treatments
- Inflammasome and immune disorders
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Legionella and Acanthamoeba research
- Erythrocyte Function and Pathophysiology
- S100 Proteins and Annexins
- Antifungal resistance and susceptibility
- Sarcoidosis and Beryllium Toxicity Research
- Atherosclerosis and Cardiovascular Diseases
- Bacterial Infections and Vaccines
- Phagocytosis and Immune Regulation
- Calcium signaling and nucleotide metabolism
- Renal Diseases and Glomerulopathies
- Blood properties and coagulation
- Complement system in diseases
- RNA and protein synthesis mechanisms
- Blood groups and transfusion
- Caveolin-1 and cellular processes
- Kawasaki Disease and Coronary Complications
University of Amsterdam
2014-2024
Sanquin
2014-2024
Amsterdam UMC Location University of Amsterdam
2016-2020
National Institute for Public Health and the Environment
2008-2010
Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding p40phox subunit phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families 8 countries. These display different in-frame or out-of-frame that are homozygous 11 and compound heterozygous another. When overexpressed NB4 neutrophil-like cells EBV-transformed B vitro, mutant alleles were found to be LOF, with exception p.R58C c.120_134del alleles,...
Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible life-threatening infections. Over course 30 years, we diagnosed CGD in 84 from 61 families using functional, molecular, and studies. The incidence Israel 1.05 per 100,000 live-births Jewish population 1.49 Israeli Arab...
Chronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results severe and life-threatening infections affected children. Single center studies from India have shown proportion of autosomal recessive (AR) CGD more than reported the West. Further, patients high mortality rates due to late referrals difficulties accessing appropriate treatment. However, there lack multicentric collaborative data on India.To describe infection patterns, immunological,...
The alternative pathway (AP) of complement activation is consistently active, keeping the system primed for immediate response. This constant "tick-over" mechanism regulated by factor H (FH) protein family, which encompasses seven highly related proteins: FH, FHL-1, and five FH-related (FHR-1 to -5) proteins. current model that FHR proteins compete with FH FHL-1 fine-tune their activities, though exact role remains unclear. Genetic studies this complex locus measurement individual members...
Whooping cough caused by Bordetella pertussis in humans, is re-emerging many countries despite vaccination. Several studies have shown that significant shifts occurred the B. population resulting antigenic divergence between vaccine strains and circulating suggesting pathogen adaptation. In Netherlands, resurgence of associated with rise an altered promoter region for toxin (ptxP3). We used Multi-Locus Sequence Typing (MLST), Multiple-Locus Variable Number Tandem Repeat Analysis (MLVA)...
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...
Summary Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent poses the risk of alloimmunization. On average, 30% SCD will alloimmunize while other patient groups form antibodies less frequently. Identification genetic markers may help to predict which are at alloantibodies. The aim this study was evaluate whether variations in Toll‐like receptor pathway or genes previously associated with antibody‐mediated conditions red (RBC)...
Hermansky-Pudlak syndrome type 2 (HPS2) is a caused by mutations in the beta-3A subunit of adaptor protein (AP)-3 complex (AP3B1 gene). We describe five unreported cases with four novel mutations, one which aberrant pre-mRNA splicing. A point mutation c.2702C>G exon 23 AP3B1 gene deletion 112 bp mRNA two siblings. This activates cryptic donor splice site that overrules wild-type this exon. Three other were identified, is, nonsense c.716G>A (p.Trp239Ter), 1-bp and 4-bp c.177delA...
Abstract Leukocyte adhesion deficiency type I is a rare primary immunodeficiency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte 1 (LAD-1). Targeted next-generation sequencing was performed either panel comprising 266 genes or small LAD-panel consisting five for genetic analysis. To measure expression level integrins on surface, flow cytometry analysis performed. The median age at diagnosis 3...
Mutations that impair expression or function of the components phagocyte NADPH oxidase complex cause chronic granulomatous disease (CGD), which is associated with life-threatening infections and dysregulated inflammation. In five CGD patients from four consanguineous families two different ethnic backgrounds, we found similar genomic homozygous deletions 1,380 bp comprising exon 5 NCF2, could be traced to Alu-mediated recombination events. cDNA sequencing showed in-frame phase zero 5,...