A5024437085- Ocular Diseases and Behçet’s Syndrome
- Systemic Lupus Erythematosus Research
- interferon and immune responses
- Autoimmune and Inflammatory Disorders Research
- Immune Cell Function and Interaction
- Inflammasome and immune disorders
- Retinal Diseases and Treatments
- Retinoids in leukemia and cellular processes
- Retinal Development and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Receptors and Signaling
- Immunotherapy and Immune Responses
- Retinal and Optic Conditions
- Adipose Tissue and Metabolism
- Otitis Media and Relapsing Polychondritis
- Immunodeficiency and Autoimmune Disorders
- Lymphoma Diagnosis and Treatment
- Folate and B Vitamins Research
- Atherosclerosis and Cardiovascular Diseases
- T-cell and Retrovirus Studies
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Galectins and Cancer Biology
- Vasculitis and related conditions
- MicroRNA in disease regulation
University Medical Center Utrecht
2016-2025
Utrecht University
2016-2024
Peter MacCallum Cancer Centre
2015
Genmab (Netherlands)
2014
Oncode Institute
2010
The Netherlands Cancer Institute
2010
Oregon Health & Science University
2009
Diagnosis of complex disease and response to treatment is often associated with multiple indicators, both clinical laboratorial. With the use biomarkers, various mechanisms have been unraveled which can lead better faster diagnosis, predicting monitoring new drug development. introduction multiplex technology for immunoassays growing awareness role immune-monitoring during therapeutic interventions it now possible test large numbers soluble mediators in small sample volumes. However,...
Objective Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms juvenile idiopathic arthritis ( JIA ). The disease mechanisms predisposing only subgroup uveitis are unknown. This study was undertaken identify genetic susceptibility loci for in , using genome‐wide association 522 . Methods Two cohorts patients ophthalmologic follow‐up data were genotyped. Data then imputed imputation reference panel, and an HLA ‐specific panel used imputing...
Abstract The function of the tumor suppressor p53 is universally compromised in cancers. It most frequently mutated gene human cancers (reviewed). In cases where not mutated, alternative regulatory pathways inactivate its suppressive functions. This primarily achieved through elevation expression key inhibitors p53: Mdm2 or Mdmx (also called Mdm4) breast cancer (BrCa), frequency mutations varies markedly between different subtypes, with basal-like BrCas bearing a high mutations, whereas...
Purpose: To determine the profile of inflammation-related proteins and complement system factors in plasma CRB1-associated inherited retinal dystrophies (CRB1-IRDs). Methods: We used Olink Explore 384 Inflammation II panel for targeted proteomics 30 cases 29 controls (cohort I) to identify immune pathways involved CRB1-IRDs. Genotyping was performed cohort I a second 123 patients from 14 countries 1292 II). Results: A significant shift cascade observed proteomes CRB1-IRD (enrichment cascade,...
Childhood uveitis is a vision-threatening inflammatory eye disease commonly attributed to juvenile idiopathic arthritis (JIA). The pathogenesis poorly understood, which makes clinical management challenging. We analyzed soluble mediators in ocular fluid (aqueous humor [AqH]) and serum from children with JIA-associated common childhood identify potential biomarkers investigate the microenvironment of this sight-threatening disease.AqH (n = 73) paired 66) samples were for 51 inflammation by...
Abstract Background The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of lesions that arise during replication or after exogenous damage. FA displays synthetic lethal relationship with certain genes such as ATM (Ataxia Telangectasia Mutated) are frequently mutated tumors. Thus, inhibition FANCD2 monoubiquitylation (FANCD2-Ub), key step pathway, might target tumor cells defective through interaction. Curcumin was previously identified weak...
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...
Background: Type I interferons (IFNs) promote the expansion of subsets CD1c+ conventional dendritic cells (CD1c+ DCs), but molecular basis DCs involvement in conditions not associated without elevated type IFNs remains unclear. Methods: We analyzed from two cohorts non-infectious uveitis patients and healthy donors using RNA-sequencing followed by high-dimensional flow cytometry to characterize DC populations. Results: report that pool with is skewed toward a gene module chemokine receptor...
PURPOSE.The cause of noninfectious uveitis (NIU) is poorly understood but considered to be mediated by a complex interplay between genetic, environmental, and-relatively unexplored-epigenetic factors.MicroRNAs (miRNAs) are noncoding small RNAs that important epigenetic regulators implicated in pathologic signaling.Therefore, we mapped the circulating miRNA-ome NIU patients and studied miRNA perturbations within broader context immune system.METHODS.We designed strategy robustly identify...
Purpose: Eye inflammation may occur in patients with inherited retinal dystrophies (IRDs) and is seen frequently IRDs associated mutations the CRB1 gene. The purpose of this study was to determine types inflammatory cells involved IRDs, by deep profiling composition peripheral blood mononuclear a CRB1-associated IRD. Methods: This included 33 an IRD confirmed 32 healthy controls. A 43-parameter flow cytometry analysis performed on isolated from venous blood. FlowSOM manual Boolean...
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...
Background: Non-infectious uveitis (NIU) is a severe intra-ocular inflammation, which frequently requires prompt systemic immunosuppressive therapy (IMT) to halt the development of vision-threatening complications. IMT considered when NIU cannot be treated with corticosteroids alone, unpredictable in advance. Previous studies have linked blood cell subsets glucocorticoid sensitivity, suggests that composition leukocytes may early identify patients will require IMT. Objective: To map...
This study was undertaken to identify key disease pathways driving conventional dendritic cell (cDC) alterations in systemic sclerosis (SSc).Transcriptomic profiling performed on peripheral blood CD1c+ cDCs (cDC2s) isolated from 12 healthy donors and 48 patients with SSc, including all major subtypes. We differential expression analysis for the different SSc subtypes uncover genes dysregulated SSc. To biologically relevant pathways, we built a gene coexpression network using weighted...
Early identification of patients with noninfectious uveitis requiring steroid-sparing immunomodulatory therapy (IMT) is currently lacking in objective molecular biomarkers. We evaluated the proteomic signature at onset disease and associated clusters need for IMT during course disease.Multicenter cohort study.Two hundred thirty treatment-free active uveitis.We used aptamer-based proteomics (n = 1305 proteins) a bioinformatic pipeline as stratification tool to define serum protein network...
Abstract Birdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive individuals and could be considered prototypic member of the recently proposed “MHC-I-opathy” family. Genetic studies have pinpointed ERAP1 ERAP2 genes as shared associations across MHC-I-opathies, which suggests ERAP dysfunction may root cause for MHC-I-opathies. We mapped haplotypes in 84 Dutch cases 890 controls. identified association at variant rs10044354, mediated marked increase expression. also...
Non-Hodgkin orbital lymphoma (NHOL) and idiopathic inflammation (IOI) are common conditions with largely unknown pathophysiology that can be difficult to diagnose. In this study we aim identify serum miRNAs associated NHOL IOI. We performed OpenArray® miRNA profiling in 33 patients controls. Differentially expressed were technically validated across technology platforms replicated an additional cohort of 32 identified independently a profile was remarkably similar IOI characterized by...
Type I interferon switches the receptor CD200R from inhibiting to potentiating inflammatory responses in immune cells.
Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes peripheral blood leukocyte composition, but their significance for AMD unclear. We aimed to determine immune cell populations patients. A standardized 31-parameter flow cytometry analysis was conducted on mononuclear cells from 59 patients with early and advanced 39 controls without AMD, all older than 65 years. Fundus photography optical coherence...
Purpose: Classical alleles of the human leukocyte antigen (HLA) complex have been linked to specific entities pediatric noninfectious uveitis, yet genetic predisposition encoded by HLA super-locus across patient population remains understudied. Methods: We performed next-generation full-length sequencing HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1 in 280 cases. Dense genotype data from 499 Dutch controls Genome Netherlands were imputed using an HLA-specific reference panel (n =...