- Salivary Gland Disorders and Functions
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Rheumatoid Arthritis Research and Therapies
- Salivary Gland Tumors Diagnosis and Treatment
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Systemic Sclerosis and Related Diseases
- Chemokine receptors and signaling
- Dermatology and Skin Diseases
- Galectins and Cancer Biology
- Lymphatic System and Diseases
- Autoimmune and Inflammatory Disorders Research
- Immune Response and Inflammation
- Oral Health Pathology and Treatment
- Cytokine Signaling Pathways and Interactions
- Osteoarthritis Treatment and Mechanisms
- Diabetes and associated disorders
- Psoriasis: Treatment and Pathogenesis
- Platelet Disorders and Treatments
- Toxin Mechanisms and Immunotoxins
- Glycosylation and Glycoproteins Research
- Inflammatory Myopathies and Dermatomyositis
- Urticaria and Related Conditions
University Medical Center Utrecht
2016-2025
Utrecht University
2001-2025
Abstract Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved tertiary structure formation have been identified, cellular sources temporal spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, transcriptomics proteomics minor salivary glands patients with Sjogren’s disease Sicca Syndrome, ex-vivo functional studies to construct a map key components function structures. We...
Abstract Objective We previously demonstrated that CD4+,CD25+ regulatory T (Treg) cells are present in increased numbers the synovial fluid (SF) of rheumatoid arthritis (RA) patients and display enhanced suppressive activity as compared with their peripheral blood (PB) counterparts. Despite presence these immunoregulatory RA, chronic inflammation persists. The purpose study was to investigate whether particular proinflammatory mediators associated RA could abrogate Treg–mediated suppression....
To investigate the prognostic value of lymphocytic focus score (LFS) and percentages IgA+, IgM+ IgG+ plasma cells for disease severity primary Sjögren syndrome (pSS).Medical charts 174 pSS patients were retrospectively analysed, comparing histology results (LFS cells) with outcomes as non-Hodgkin lymphoma (NHL) clinical scores including cumulative EULAR (European League against Rheumatism) activity index (ESSDAI) total number extraglandular manifestations.The mean LFS was significantly...
To evaluate the performance of individual biomarkers and a multi-biomarker disease activity (MBDA) score in early rheumatoid arthritis (RA) patient population from computer assisted management (CAMERA) study.Twenty were measured CAMERA cohort, which patients treated with either intensive or conventional methotrexate-based treatment strategies. The MBDA was calculated using concentrations 12 (SAA, IL-6, TNF-RI, VEGF-A, MMP-1, YKL-40, MMP-3, EGF, VCAM-1, leptin, resistin CRP) according to...
Innate lymphoid cells (ILCs) are a recently discovered group of that essential to epithelial homeostasis and implicated in psoriasis pathogenesis, yet they have never been reported psoriatic arthritis (PsA).ILC classes subsets were characterized the peripheral blood (PB) healthy controls, patients with psoriasis, PsA synovial fluid (SF) rheumatoid (RA). Cell surface marker expression intracellular cytokine production following stimulation analyzed using flow cytometry.ILCs identified SF...
Fibrosis is a major cause of mortality worldwide, characterized by myofibroblast activation and excessive extracellular matrix deposition. Systemic sclerosis prototypic fibrotic disease in which CXCL4 increased strongly correlates with skin lung fibrosis. Here we aim to elucidate the role fibrosis development. levels are multiple inflammatory mouse models, and, using CXCL4-deficient mice, demonstrate essential promoting events skin, lungs, heart. Overexpressing human mice aggravates, whereas...
Abstract Objective. Inflammation‐induced articular cartilage degradation is a major problem in rheumatoid arthritis (RA). Type 1 T cell activity (characterized by interferon‐γ/interleukin‐2 [IL‐2] production), and consequently, the production of proinflammatory cytokines IL‐1 tumor necrosis factor α (TNFα), have been reported to play role damage. IL‐10 IL‐4, both produced type 2 cells, are with capacity down‐regulate responses. The present study was undertaken investigate way which these...
Abstract Leukocyte-associated Ig-like receptor (LAIR)-1 is a collagen-receptor that inhibits immune cell function upon collagen binding. Next to LAIR-1, the human genome encodes LAIR-2, putative soluble homolog. In this study we show, for first time, LAIR-2 gene broadly transcribed in PBMC, mirroring expression profile of LAIR-1. protein expressed as exhibiting high affinity various molecules which it binds hydroxyproline-dependent manner. vitro stimulation PBMC induces secretion LAIR-2. We...
Abstract Objective To study the expression levels and immunostimulatory capacities of interleukin‐7 (IL‐7) in primary Sjögren's syndrome. Methods Labial salivary gland (LSG) IL‐7 was determined by immunohistochemistry, using a quantitative scoring system, 30 patients with sicca syndrome: 15 syndrome (SS) non‐SS The correlation LSGs parameters local peripheral disease studied, serum were determined. Additionally, effects on cytokine production blood mononuclear cells (PBMCs) from SS vitro...
Increased release of neutrophil extracellular traps (NETs) is implicated in the activation plasmacytoid dendritic cells, vascular disease and thrombosis SLE APS. However, studies comparing NET between patients with APS are lacking. Here we evaluated plasma-induced a large cohort SLE, + primary relation to clinical serological parameters.Neutrophils from healthy controls were exposed plasma heterologous (n = 27) or 55), 38) (PAPS) 28) was quantified by immunofluorescence. In subset patients,...
MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature serum of systemic sclerosis (SSc) patients further assessed their expression early stages disease.The levels 758 miRNAs were evaluated 26 SSc compared to 9 healthy controls by using an Openarray platform. Three examined additional cohort 107 24 donors single qPCR. MiR-483-5p was analysed with localized...
Chronic pain is a major clinical problem that difficult to treat and requires novel therapies. Although most therapies primarily target neurons, neuroinflammatory processes characterized by spinal cord dorsal root ganglion production of proinflammatory cytokines play an important role in persistent states represent potential therapeutic targets. Anti-inflammatory are attractive candidates regulate aberrant processes, but the these as stand-alone drugs limited. Their optimal function...
Objective evaluation of disease activity is challenging in patients with juvenile dermatomyositis ( DM ) due to a lack reliable biomarkers, but it crucial avoid both under‐ and overtreatment patients. Recently, we identified 2 proteins, galectin‐9 CXCL 10, whose levels are highly correlated the extent activity. This study was undertaken validate 10 as biomarkers for , assess their specificity potency predicting occurrence flares. Methods Levels were measured by multiplex immunoassay serum...
The interferon (IFN) signature is related to disease activity and vascular in systemic lupus erythematosus (SLE) antiphospholipid syndrome (APS) represents a promising therapeutic target. Quantification of the IFN currently performed by gene expression analysis, limiting its current applicability clinical practice. Therefore, objective this study was establish an easy measure biomarker for signature.Serum levels galectin-9, CXCL-10 (IP-10) tumour necrosis factor receptor type II (TNF-RII)...
Plasmacytoid dendritic cells (PDCs) are a critical source of type I interferons (IFNs) that can contribute to the onset and maintenance autoimmunity. Molecular mechanisms leading PDC dysregulation persistent IFN signature largely unexplored, especially in patients with systemic sclerosis (SSc), disease which PDCs infiltrate fibrotic skin lesions produce higher levels IFNα than those healthy controls. This study was undertaken investigate potential microRNA (miRNA)-mediated epigenetic...
Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune-cells in 169 patients with these SADs 44 healty controls (HC) using mass-cytometry assessed diagnostic value results. Alterations immune-cell subsets were present all compared to HC. Most alterations, including a decrease CD56hi NK-cells SSc IgM+ Bcells pSS, disease...
<b>Background:</b> A large number of activated T cells are found in the joints patients with rheumatoid arthritis (RA). Interleukin 7 (IL7), a cell growth factor and regulator Th1 Th2 cytokine production, is produced by synoviocytes from RA. <b>Objective:</b> To investigate effect on proinflammatory production synovial fluid mononuclear (SFMC) mechanism which IL7 influences CD4+ activity <b>Methods:</b> In cross sectional group RA, levels were compared those healthy controls related to...
Abstract Objective To determine the level of intraarticular expression interleukin‐7 (IL‐7) in patients with rheumatoid arthritis (RA) and to investigate mechanisms by which IL‐7 facilitates activation CD4+ T cells monocyte/macrophages RA. Methods levels were measured synovial fluid obtained from RA osteoarthritis (OA). Immunohistologic analysis was used assess tissue Proliferation markers determined order measure effect on mononuclear cells, isolated peripheral blood fluid. Cocultures...
<b>Background:</b> For invalidating symptoms in primary Sjögren's syndrome (pSS), there is still a need for easy-to-administer, cost-effective and well-tolerated systemic treatment. Leflunomide (LEF) structurally unrelated to other immunomodulatory drugs might be efficacious pSS, given its characteristic immunoregulatory modes of action. <b>Objective:</b> To investigate the safety efficacy LEF pSS phase II open-label pilot study. <b>Methods:</b> 15 patients with early active disease received...
To study the effects of interleukin-7 receptor α-chain (IL-7Rα) blockade on collagen-induced arthritis (CIA) and to investigate T cell numbers, activity, levels proinflammatory mediators.We studied effect anti-IL-7Rα antibody treatment inflammation joint destruction in CIA mice. Numbers thymocytes, splenocytes, subsets, B cells, macrophages, dendritic cells were assessed. Cytokines indicative Th1, Th2, Th17 activity several mediators assessed by multianalyte profiling paw lysates. In...