A5038246024- Genomic variations and chromosomal abnormalities
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Genomics and Rare Diseases
- Prenatal Screening and Diagnostics
- Genomics and Chromatin Dynamics
- Inflammasome and immune disorders
- RNA modifications and cancer
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- Congenital heart defects research
- Galectins and Cancer Biology
- Acute Lymphoblastic Leukemia research
- interferon and immune responses
- Acute Myeloid Leukemia Research
- Chromosomal and Genetic Variations
- Cytomegalovirus and herpesvirus research
- Autoimmune and Inflammatory Disorders Research
- Chronic Lymphocytic Leukemia Research
- Blood disorders and treatments
- Otitis Media and Relapsing Polychondritis
- Genetic Syndromes and Imprinting
- Ocular Diseases and Behçet’s Syndrome
Utrecht University
2014-2023
University Medical Center Utrecht
2011-2023
Heidelberg University
2023
University Hospital Heidelberg
2023
Wilhelmina Children's Hospital
2016-2018
Medical Genetics Center
2014-2016
Erasmus MC - Sophia Children’s Hospital
2010
Erasmus MC
2010
Leiden University Medical Center
2005-2009
Abstract Retroviral transfer of T-cell receptors (TCR) to peripheral blood–derived T cells generates large numbers with the same antigen specificity, potentially useful for adoptive immunotherapy. One drawback this procedure is formation mixed TCR dimers unknown specificities due pairing endogenous and introduced chains. We investigated whether γδ can be an alternative effector population gene because γδTCR not able form αβTCR. Peripheral were transduced human leukocyte (HLA) class I– or HLA...
Objective Human leukocyte antigen (HLA)‐DRB1*15:01 has been recently associated with interstitial lung disease (LD), eosinophilia, and drug reactions in systemic juvenile idiopathic arthritis (sJIA). Additionally, genetic variants IL1RN have linked to poor response anakinra. We sought reproduce these findings a prospective cohort study of patients new‐onset sJIA treated anakinra as first‐line therapy. Methods HLA risk alleles were identified via whole‐genome sequencing. Treatment responses...
The successful application of T cell-based immunotherapeutic applications depends on the availability large numbers cells with desired Ag specificity and phenotypic characteristics. Engineering TCR-transferred lymphocytes is an attractive strategy to obtain sufficient choice. However, introduction additional TCR chains into leads generation unknown specificity, due formation mixed dimers between endogenous introduced chains. such potentially autoaggressive may be prevented by using...
Abstract Killer Ig-like receptors (KIR) are expressed by human NK cells and T cells. Although Ag-specific cytolytic activity cytokine production of KIR+ can be inhibited KIR ligation, the effect on proliferation is unclear. have been reported to a general proliferative defect. To investigate whether represent end-stage dysfunctional cells, we characterized CMV-specific in allogeneic stem cell transplantation patients healthy donors. In both donors, significant percentage was detected at...
Birdshot Uveitis (BU) is a blinding inflammatory eye condition that only affects HLA-A29-positive individuals. Genetic association studies linked ERAP2 with BU, an aminopeptidase which trims peptides before their presentation by HLA class I at the cell surface, suggests ERAP2-dependent peptide HLA-A29 drives pathogenesis of BU. However, it remains poorly understood whether effects on peptidome are distinct from its effect other allotypes. To address this, we focused immunopeptidome in...
Inborn errors of immunity (IEI) are a heterogeneous group disorders, affecting different components the immune system. Over 450 IEI related genes have been identified, with new continually being recognized. This makes early application next-generation sequencing (NGS) as diagnostic method in evaluation promising development. We aimed to provide an overview yield and time diagnosis cohort patients suspected evaluated by NGS based panel trajectory multicenter setting Netherlands.We performed...
Genomic rearrangements are a common cause of human congenital abnormalities. However, their origin and consequences poorly understood. We performed molecular analysis two patients with disease who carried de novo genomic rearrangements. found that the in both hit genes recurrently rearranged cancer (ETV1, FOXP1, microRNA cluster C19MC) drive formation fusion similar to those described cancer. Subsequent large set 552 germline underlying disorders revealed enrichment for overlap somatic...
Several cases have been reported of patients with a ring chromosome 18 replacing one the normal chromosomes 18. Less common are supernumerary High resolution whole genome examination in multiple congenital abnormalities might reveal cytogenetic an unexpected complexity.We report 24 years old male patient lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra radial dysplasia, and hypoplastic thumb. Some anomalies overlap VACTERL association....
Single-nucleotide polymorphisms (SNPs) near the ERAP2 gene are associated with various autoimmune conditions, as well protection against lethal infections. Due to high linkage disequilibrium, numerous trait-associated SNPs correlated expression; however, their functional mechanisms remain unidentified. We show by reciprocal allelic replacement that expression is directly controlled splice region variant rs2248374. However, disease-associated variants in downstream LNPEP promoter...
First, to determine the infant mortality rate (IMR) for Dutch patients with isolated oral clefts (OC) as well seen in association other malformations. Second, conduct a similar analysis per cleft type: lip or without palate (CP), CP (including Robin sequence). Third, examine underlying causes of death.A retrospective review charts OC born period 1997-2011 and treated three regional centers Netherlands.One thousand five hundred thirty were during study centers. The overall IMR all was 2.09%,...
EVI1 (3q26.2) is a member of the SET/PR domain family transcription factors and contains two domains zinc finger (ZF) DNA binding motifs, one at N-terminus (ZF1) C-terminus (ZF2), C-terminal acidic amino acid cluster (AD). The MDS1/EVI1 locus gives rise to
We describe a 13-year-old boy with developmental delay and proximal muscle weakness who has monosomy 20 mosaicism in blood skin cells. Because of asymmetric features (difference foot size, slightly intergluteal cleft), we performed extensive cytogenetic studies peripheral skin. In cultured uncultured lymphocytes, found 0.9 6.5% cells 20, respectively. addition, 3.3% fibroblasts 1.5% buccal mucosa had 20. This is the fifth patient published this chromosomal condition. These patients show...
Abstract Single nucleotide polymorphisms (SNP) near the ERAP2 gene are associated with autoimmune conditions such as Crohn’s disease , and birdshot chorioretinopathy well protection against lethal infections, including Black Death . Due to high linkage disequilibrium (LD), a great number of trait-associated SNPs correlated expression, however their functional mechanisms remain unidentified. We used genome editing genomics identify causal variants that obscured by LD. demonstrate reciprocal...
In vitro stimulation of human female T cells with male HLA-identical dendritic resulted in the generation HLA-DQB1*0501/0502-restricted minor histocompatibility H-Y antigen-specific CD4+ cell clones. Two clones generated from different pairs were analyzed. Use HLA-DQ5-expressing Epstein-Barr virus transformed B lymphoblastoid lines transfected various genes and loaded overlapping peptides demonstrated that both are specific for a peptide encoded by DDX3Y. Previously, an HLA-DQ5-restricted...
Abstract Worldwide, there are large inequalities in genetic service delivery. In 2011, we established a bi‐annual joint pediatric‐genetics clinic with visiting clinical geneticist the Dutch Caribbean. This retrospective study evaluates yield of diagnostic testing and utility diagnosis for patients rare diseases on these relatively isolated, resource‐limited islands. A total 331 that were referred to between November 2011 2019 had included this study. 508 tests performed patients. Microarray,...