A5051691526- Spondyloarthritis Studies and Treatments
- Mast cells and histamine
- Rheumatoid Arthritis Research and Therapies
- Autoimmune and Inflammatory Disorders Research
- Psoriasis: Treatment and Pathogenesis
- Urticaria and Related Conditions
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Bone Metabolism and Diseases
- Lymphoma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Multiple Myeloma Research and Treatments
- Wnt/β-catenin signaling in development and cancer
- Dermatology and Skin Diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Single-cell and spatial transcriptomics
- Osteoarthritis Treatment and Mechanisms
- Cytokine Signaling Pathways and Interactions
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- T-cell and Retrovirus Studies
- HER2/EGFR in Cancer Research
- Inflammasome and immune disorders
Stanford University
2024
Leiden University Medical Center
2024
University of Amsterdam
2008-2018
Center for Rheumatology
2014-2018
Graduate School USA
2017
Amsterdam UMC Location University of Amsterdam
2008-2016
Abstract Objective Studies comparing spondylarthritis (SpA) to rheumatoid arthritis (RA) synovitis suggest that innate immune cells may play a predominant role in the pathogenesis of SpA. Recent observations have indicated marked synovial mast cell infiltration psoriatic We therefore undertook present study investigate potential contribution inflammation Methods Synovial tissue and fluid were obtained from patients with either nonpsoriatic or SpA (n = 82) RA 50). biopsy was analyzed by...
The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the neoplasms related to viral vector integration, is an emerging concern.
Abstract Objective Peripheral spondylarthritis (SpA) is characterized by macrophages that express CD163, a marker of alternative activation (M2). The purpose this study was to assess whether differential infiltration with macrophage subsets associated different local inflammatory milieu in SpA as compared rheumatoid arthritis (RA). Methods effect and RA synovial fluid (SF) on polarization tested vitro normal peripheral blood monocytes. SF levels classically activated (M1)–derived...
Abstract Introduction Synovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets this process remains largely unknown. The main vitro polarized are classically (M1) and alternatively (M2) activated macrophages, latter comprising interleukin (IL)-4 IL-10 cells. Here, we aimed to evaluate polarization status synovial spondyloarthritis (SpA) rheumatoid arthritis (RA). Methods Expression markers on peripheral blood...
Abstract IL-17A, a major proinflammatory cytokine, can be produced by variety of leukocytes, but its exact cellular source in human inflammatory diseases remains incompletely understood. IL-17A protein is abundantly found mast cells tissues, such as inflamed synovium, surprisingly, mechanistic murine studies failed to demonstrate production cells. Here, we that primary tissue do not produce themselves actively capture exogenous through receptor-mediated endocytosis. The stored intracellular...
Abstract Objective Spondylarthritis (SpA) and rheumatoid arthritis (RA) have different patterns of bone damage, with more pronounced erosions in RA. The RANK/RANKL/osteoprotegerin (OPG) system plays a central role resorption by promoting the maturation activation osteoclasts. To assess potential this distinct phenotype, we studied synovial expression these mediators SpA RA peripheral synovitis. Methods Synovial biopsy specimens were obtained from actively inflamed joints 35 patients 19...
Abstract Objective The molecular processes driving the distinct patterns of synovial inflammation and tissue remodeling in spondylarthritis (SpA) as compared to rheumatoid arthritis (RA) remain largely unknown. Therefore, we aimed identify novel unsuspected disease‐specific pathways SpA by a systematic unbiased gene expression analysis. Methods Differentially expressed genes were identified pan‐genomic microarray confirmed quantitative polymerase chain reaction immunohistochemical analyses...
Abstract Introduction The aim of the study was to investigate synovial immunopathology differences between early Behçet disease (BD) and psoriatic arthritis (PsA). Methods Needle arthroscopy an inflamed knee joint performed in patients with untreated BD (n = 8) PsA 9). Synovial fluid (SF) collected for cytokines, perforin, granzyme analysis. Eight biopsies per patient were obtained immunohistochemical analysis cellular infiltrate (T cells, natural killer macrophages, B plasma mast...
Abstract Objective Cadherin 11 expressed on fibroblast‐like synoviocytes (FLS) plays a key role in normal synovial architecture. The purpose of this study was to examine the expression cadherin human synovitis. Methods biopsy samples from patients with various types arthritis and lung interstitial pneumonitis (IP) examined by immunostaining. regulation FLS assessed quantitative reverse transcription–polymerase chain reaction analysis Western blotting. Therapeutic modulation before after...
Clinical trials of the anti-interleukin-17A (anti-IL-17A) antibody secukinumab have demonstrated a crucial role cytokine IL-17A in pathogenesis spondyloarthritis (SpA); however, its cellular source this condition remains matter controversy. Group 3 innate lymphoid cells (ILC3s) been recently identified as potent producers proinflammatory cytokines, including and IL-22, number different tissues. This study was undertaken to characterize presence composition ILCs, investigate whether these are...
Abstract Objectives Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent vitro study showed that tissue-derived can capture and release exogenous IL-17A. The present aimed to investigate if this mechanism could contribute Methods Potential activation by IL-17A was assessed gene expression analysis the Laboratory Allergic Diseases 2 (LAD2) cell line. presence IL-17A-positive immunohistochemistry synovial obtained before after secukinumab treatment, as well...
To evaluate the immunomodulating and clinical effects of nilotinib, a tyrosine kinase inhibitor, in proof-of-concept study spondyloarthritis (SpA) assessing mast cell as potential novel therapeutic target this disease.Twenty eight patients with active peripheral (pSpA) and/or axial SpA (axSpA) were included randomized, double-blind, placebo-controlled trial (Trial registration: Trialregister.nl NTR2834). Patients treated 1:1 nilotinib or placebo for 12 weeks, followed by an open label...
<h3>Background</h3> Spondyloarthritis (SpA) is a major form of chronic inflammatory arthritis characterized by inflammation axial and peripheral joints pathologic new bone formation leading to ankylosis. Consistent genetic, experimental, clinical evidence indicates that IL-23/IL-17 immune axis plays pivotal role in the pathophysiology SpA. It remains, however, unknown which IL-23 responsive cells are cellular source IL-17 Innate lymphoid (ILCs) an emerging family innate produce various...
<h3>Background</h3> Immunopathological studies on synovitis recently identified the mast cell as potential novel therapeutic target in spondyloarthritis (SpA).[1] Mast cells can be targeted by inhibiting signalling of c-Kit, which is one targets tyrosine kinase inhibitor nilotinib. <h3>Objectives</h3> To evaluate immunomodulating and clinical effects nilotinib treatment SpA. <h3>Methods</h3> 28 patients with active peripheral and/or axial SpA were included a randomized, double-blind,...
<h3>Background</h3> IL-17A plays an important role in rheumatic diseases, like rheumatoid arthritis and spondyloarthritis. Direct analysis of inflamed synovial tissue revealed abundant presence IL-17A-positive mast cells. <h3>Objectives</h3> As cells are not known to produce mice, we aimed investigate the mechanism expression by human <h3>Methods</h3> IL-17A, IL-17F RORC mRNA protein was assessed ex vivo after PMA/ionomycine stimulation primary sorted from tonsils. Internalization exogenous...
Background The cellular and molecular pathways driving synovial inflammation stromal remodeling in spondyloarthritis (SpA) remain largely unknown. As SpA rheumatoid arthritis (RA) show clearly distinct patterns of structural remodelling, we conducted this study to identify specific for synovitis by an unbiased microarray screening approach the inflamed tissue both conditions.