Sebastiaan J Vastert

Sebastiaan J Vastert
University Medical Center Utrecht | UMC Utrecht · Division of Pediatrics

MD, PhD

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189
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Publications

Publications (189)
Article
Full-text available
Despite a rapidly accumulating clinical experience with autologous stem cell transplantation (ASCT) as a treatment for severe refractory autoimmune disease, data on the mechanisms by which ASCT induces immune tolerance are still very scarce. In this study it is shown that ASCT restores immunologic self-tolerance in juvenile idiopathic arthritis (JI...
Article
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Autologous stem cell transplantation (ASCT) has been described since 1997 as a treatment for children with polyarticular or systemic juvenile idiopathic arthritis (JIA) resistant to conventional treatment and anti-tumor necrosis factor- agents.1, 2
Article
Systemic-onset juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by arthritis and systemic features. Its pathogenesis is still largely unknown. It is characterized immunologically by natural killer (NK) cell dysfunction and cytokine signatures that predominantly feature interleukin-1 (IL-1), IL-6, and IL-18. Since IL-18 can...
Article
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Macrophage activation syndrome (MAS) in systemic onset juvenile idiopathic arthritis (SoJIA) is considered to be an acquired form of familial haemophagocytic lymphohistiocytosis (fHLH). FHLH is an autosomal recessive disorder, characterized by diminished NK cell function and caused by mutations in the perforin gene (PRF1) in 20-50% of patients. Int...
Article
Does age substantially affect the emergence of human immune-mediated arthritis? Children do not usually develop immune-mediated articular inflammation during their first year of life. In patients with juvenile idiopathic arthritis, this apparent 'immune privilege' disintegrates, and chronic inflammation is associated with variable autoantibody sign...
Article
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Objective This study investigates the relationship of child, caregiver, and caring context measurements with the care-related quality of life (CRQoL) and health-related quality of life (HRQoL) of caregivers of children with juvenile idiopathic arthritis (JIA). Methods We performed a cross-sectional analysis of baseline data on caregivers of childr...
Article
Objectives Gut inflammation commonly occurs in axial spondyloarthritis (axSpA), and is linked to disease activity and outcome. Given the role of IgA in mucosal immunity, we explored the association between anti-CD74 IgA antibodies, gut inflammation and axSpA. Methods Anti-CD74 IgA was measured by ELISA in serum samples of axSpA patients (fulfillin...
Article
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Systemic juvenile idiopathic arthritis (sJIA, also called Still's disease) is a rare childhood auto‐inflammatory disease with significant morbidity. This case report illustrates the clinical course and highlights diagnostic challenges. FDG‐PET/CT imaging may be beneficial in the diagnostic process for some cases, in order to achieve rapid diagnosis...
Article
Objective To investigate medication prescription patterns among children with juvenile idiopathic arthritis (JIA), including duration, sequence and reasons for medication discontinuation. Methods This study is a single-center, retrospective analysis of prospective data from electronic medical records of JIA patients receiving systemic therapy aged...
Article
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Objective Pharmacological treatment is a cornerstone of care for children with juvenile idiopathic arthritis (JIA). The objective of this study is to evaluate prescription patterns of conventional and biologic disease modifying anti-rheumatic drugs (c-DMARDs and b-DMARDs) for patients with JIA. Methods We conducted a retrospective cohort study of...
Preprint
Systemic juvenile idiopathic arthritis (sJIA, also called Still’s disease) is a rare childhood auto-inflammatory disease with significant morbidity. This case report illustrates the clinical course and highlights diagnostic challenges. FDG-PET/CT imaging may be beneficial in the diagnostic process for some cases, in order to achieve rapid diagnosis...
Article
Background: Few studies have examined pediatric rheumatologists' approaches to treatment decision making for biologic therapy for patients with juvenile idiopathic arthritis (JIA). This study presents the qualitative research undertaken to support the development of a Best-Worst Scaling (BWS) survey for tapering in JIA. The study objectives were t...
Preprint
Objective Tregs are crucial for immune regulation, and environment-driven adaptation of effector (e)Tregs is essential for local functioning. However, the extent of human Treg heterogeneity in inflammatory settings is unclear. Methods We combined single-cell RNA- and TCR-sequencing on Tregs derived from 4-6 patients with juvenile idiopathic arthri...
Preprint
Dendritic cells (DC) are crucial for initiating and shaping immune responses. So far, little is known about heterogeneity and functional specialization of human DC subsets in (local) inflammatory conditions. We profiled conventional (c)DC1, cDC2 and monocytes based on phenotype, transcriptome and function from a local inflammatory site, namely syno...
Preprint
Autoimmune inflammation is characterized by tissue infiltration and expansion of antigen-specific T cells. Although this inflammation is often limited to specific target tissues, it remains yet to be explored whether distinct affected sites are infiltrated with the same, persistent T cell clones. Here we performed CyTOF analysis and T cell receptor...
Preprint
Upon antigen-specific T Cell Receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming. Here, we show that generation of extra-mitochondrial pyruvate is an essential step for acetyl-CoA production and subsequent H3K27ac-mediated epigenome remodeli...
Article
Objective: To evaluate the long-term safety profile of anakinra in patients with systemic juvenile idiopathic arthritis (SJIA). Methods: Data from patients with SJIA enrolled in the Pharmachild registry (NCT03932344) before 30 September 2018 and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse e...
Article
Background The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patie...
Preprint
Full-text available
How the local inflammatory environment regulates epigenetic changes in the context of autoimmune diseases remains unclear. Here we assessed the transcriptional and active enhancer profile of monocytes derived from the inflamed joints of Juvenile Idiopathic Arthritis (JIA) patients, a model well-suited for studying autoimmune diseases. RNA-sequencin...
Article
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Invariant Natural Killer T (iNKT) cells respond to the ligation of lipid antigen-CD1d complexes via their T-cell receptor and are implicated in various immunometabolic diseases. We considered that immunometabolic factors might affect iNKT cell function. To this end, we investigated iNKT cell phenotype and function in a cohort of adolescents with ch...
Article
Objectives To evaluate the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency (MKD) during the open label extension (weeks 41–113) of the randomised controlled CLUSTER trial. Methods During a 72-week period, patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks. The disease activity was...
Article
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Objective Juvenile dermatomyositis (JDM) is a rare chronic immune-mediated inflammatory disease with a predominant role for type I interferon (IFN) responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients wit...
Article
Systemic juvenile idiopathic arthritis is a distinct and heterogeneous disease presently classified under the umbrella of juvenile idiopathic arthritis, with some patients following a monophasic remitting course, whereas others have persistent disease with chronic organ- and life-threatening complications. Although biologic therapies have revolutio...
Article
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Introduction: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease, whose multifaceted care path can lead to significant expenditure for the healthcare system. We aim to assess the real-world healthcare resource use (HCRU) and associated cost for children with JIA in a single center in Canada. Methods: A single-center consecutive c...
Article
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Dermal fibroblasts are strategically positioned underneath the basal epidermis layer to support keratinocyte proliferation and extracellular matrix production. In inflammatory conditions, these fibroblasts produce cytokines and chemokines that promote the chemoattraction of immune cells into the dermis and the hyperplasia of the epidermis, two char...
Article
Background Systemic juvenile idiopathic arthritis (SJIA) is characterized by extra-articular manifestations, as fever and rash, and rarely associated by a potentially lethal complication as macrophage activation syndrome (MAS). Anakinra is a recombinant human interleukin (IL)-1 receptor antagonist whose efficacy and safety profile has been studied...
Article
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Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-d...
Article
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Objective This study aims to 1) quantify costs of hospital‐associated care for juvenile idiopathic arthritis (JIA), 2) provide insights in patient‐level variation in costs, and 3) investigate costs over time from the moment of JIA diagnosis. Results are reported for all JIA patients in general and by subtype. Methods This study is a single‐center,...
Article
Background: Cytokine storm syndromes are life-threatening complications which can occur in children with rheumatic conditions (macrophage activation syndrome, MAS), inherited cytotoxicity defects (primary haemophagocytic lymphohistiocytosis, pHLH) or in course of infection or malignancies (secondary HLH, sHLH). To adequately steer subsequent treatm...
Article
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Background Involving the end-users of scientific research (patients, carers and clinicians) in setting research priorities is important to formulate research questions that truly make a difference and are in tune with the needs of patients. We therefore aimed to generate a national research agenda for Juvenile Idiopathic Arthritis (JIA) together wi...
Article
Full-text available
T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro‐inflammatory cytokines upon re‐stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). Howe...
Article
Objective To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). Study design International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clin...
Article
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Crohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies and a tight disease control. However, it is challenging to assess the risk of relapses in individual patients. We investigated blood-based biomarkers for t...
Article
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Chronic inflammatory diseases such as rheumatoid arthritis (RA), Juvenile Idiopathic Arthritis (JIA), psoriasis, and inflammatory bowel disease (IBD) are characterized by systemic as well as local tissue inflammation, often with a relapsing-remitting course. Tissue–resident memory T cells (TRM) enter non-lymphoid tissue (NLT) as part of the anamnes...
Preprint
BACKGROUND The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patie...
Article
Full-text available
Background: This study aims to quantify medication costs in juvenile idiopathic arthritis (JIA), based on subtype. Research design and methods: This study is a single-center, retrospective analysis of prospective data from electronic medical records of JIA patients, aged 0-18 years between April 1, 2011 and March 31, 2019. Patient characteristics (...
Article
Juvenile systemic sclerosis (JSSc) is a rare disease of childhood and currently no international consensus exists with regard to its assessment and treatment. This SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) initiative, based on expert opinion informed by the best available evidence, provides recommendations for the as...
Preprint
Full-text available
Treg are critical regulators of immune homeostasis, and increasing evidence demonstrates that environment-driven Treg differentiation into effector (e)Treg is crucial for optimal functioning. However, human Treg programming under inflammatory conditions remains poorly understood. Here, we combine transcriptional and epigenetic profiling to identify...
Article
Full-text available
Purpose: Patients with juvenile idiopathic arthritis (JIA) are prone to developing chronic anterior uveitis (JIA-U+). Although several risk factors for JIA-U+ have been identified, the underlying etiology is poorly understood. Histopathological studies demonstrate B cell infiltrates in eye tissues of patients with JIA-U+. Methods: We performed t...
Preprint
Full-text available
Background: Involving the end-users of scientific research (patients, carers and clinicians) in setting research priorities is important to formulate research questions that truly make a difference and are in tune with the needs of patients. We therefore aimed to generate a national research agenda for Juvenile Idiopathic Arthritis (JIA) together w...
Preprint
Full-text available
Background Involving the end-users of scientific research (patients, carers and clinicians) in setting research priorities is important to formulate research questions that truly make a difference and are in tune with the needs of patients. We therefore aimed to generate a national research agenda for Juvenile Idiopathic Arthritis (JIA) together wi...
Article
Full-text available
IL-1 mediated auto-inflammatory diseases are characterised by episodes of unexplained fever, generalized and localized inflammation. The characteristic symptoms predominantly result from exaggerated activation of innate immune pathways. However, in some patients with typical IL-1 mediated diseases, chronic disease manifestations develop in the abse...
Article
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There are 3 recently published guidelines for the treatment of JIA. All of the guideline panels struggled to balance the desirable and undesirable effects of MTX. This resulted in a striking diversity of recommendations, clearly associated with the presence and the degree of involvement of patients and parents in the guideline process. We—a parent...
Article
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Purpose: To describe the results of tocilizumab treatment in children with refractory non-anterior uveitis. Methods: A case series of seven children with refractory non-anterior uveitis (onset ≤16 years) with leakage on fluorescein angiogram (FA) were treated with tocilizumab intravenously every 4 weeks (eight mg/kg). Minimum follow-up was 6 months...
Preprint
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Introduction/Abstract T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro 1–29 . Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idio...
Article
Full-text available
Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these being one disease-Still's disease-with different ages of onset. Anakinra was recently approved by the European Medicines Agency for Still's disease. In this review we discuss the reason...
Article
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Objectives: IgA vasculitis (IgAV, formerly known as Henoch-Schönlein purpura) is the most common cause of systemic vasculitis in childhood. To date, there are no internationally agreed, evidence-based guidelines concerning the appropriate diagnosis and treatment of IgAV in children. Accordingly, treatment regimens differ widely. The European initi...
Article
Objectives: To provide an overview of the paediatric rheumatology (PR) services in Europe, describe current delivery of care and training, set standards for care, identify unmet needs and inform future specialist service provision. Methods: An online survey was developed and presented to national coordinating centres of the Paediatric Rheumatolo...
Conference Paper
Background Impaired immunological tolerance in Juvenile Idiopathic Arthritis (JIA) is the result of a disturbed balance between regulatory T-cells (Tregs) and effector T-cells (Teffs). Restoring this balance by either enhancing the suppressive function of Tregs or inhibiting activity of pro-inflammatory Teffs seems a promising therapeutic strategy....
Conference Paper
Background Heterogeneity in response to biological medication is a major challenge in the management of Juvenile Idiopathic Arthritis (JIA) (1). Biomarkers such as cytokines or whole blood RNA expression profiles that predict therapy efficacy prior to treatment pose a solution and could enable precision medicine. It was previously demonstrated that...
Article
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Background This study aims to describe current practice in identifying and measuring health care resource use and unit costs in economic evaluations or costing studies of juvenile idiopathic arthritis (JIA). Methods A scoping review was conducted (in July 2018) in PubMed and Embase to identify economic evaluations, costing studies, or resource uti...
Article
Objectives The International League of Associations for Rheumatology classification criteria define systemic juvenile idiopathic arthritis (SJIA) by the presence of fever, rash and chronic arthritis. Recent initiatives to revise current criteria recognise that a lack of arthritis complicates making the diagnosis early, while later a subgroup of pat...
Article
Objectives: The European initiative Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) aimed to optimize care for children with rheumatic diseases. Systemic vasculitides are very rare in children. Consequently, despite recent advances, paediatric-specific information is sparse. The lack of evidence-based recommendations is a...
Article
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Objectives: The European Single Hub and Access point for paediatric Rheumatology in Europe initiative aimed to optimize care for children with rheumatic diseases. Kawasaki disease (KD) is the most common cause of acquired heart disease in children and an important cause of long-term cardiac disease into adulthood. Prompt diagnosis and treatment of...
Article
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Objective Systemic juvenile Idiopathic Arthritis (JIA) is a multifactorial autoinflammatory disease with an historically poor prognosis. With current treatment regimens, approximately half of patients still experience active disease after one year of therapy. Our treat‐to‐target approach, using recombinant interleukin‐1 receptor antagonist (rIL‐1RA...
Article
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In 2012, a European initiative called Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile localised scleroderma (JLS) is a rare disease within the group of paediatric rheumatic d...
Article
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Juvenile Idiopathic Arthritis (JIA) is characterized by a loss of immune tolerance. Here, the balance between the activity of effector T (Teff) cells and regulatory T (Treg) cells is disturbed resulting in chronic inflammation in the joints. Presently, therapeutic strategies are predominantly aimed at suppressing immune activation and pro-inflammat...
Article
Full-text available
Juvenile idiopathic arthritis (JIA) represents joint inflammation with an unknown cause that starts before the age of 16, resulting in stiff and painful joints. In addition, JIA patients often report symptoms of sickness behavior. Recent animal studies suggest that proinflammatory cytokines produce sickness behavior by increasing the activity of in...
Article
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Objectives To assess the composition of gut microbiota in Italian and Dutch juvenile idiopathic arthritis (JIA) patients at baseline, in inactive disease and persistent activity, compared to healthy controls. Methods In a prospective, multicenter, observational cohort study, fecal samples were collected of 78 Italian and 21 Dutch treatment‐naïve J...