Publications by authors named "Dik W"

In previous work we discovered that T lymphocytes play a prominent role in the rise of brain metastases of ER-negative breast cancers. In the present study we explored how T lymphocytes promote breast cancer cell penetration through the blood brain barrier (BBB). An in vitro BBB model was employed to study the effects of T lymphocytes on BBB trespassing capacity of three different breast carcinoma cell lines.

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Introduction: Severe COVID-19 is associated with reduced absolute lymphocyte counts, suggesting that lymphocyte subsets may serve as predictors of clinical outcomes in affected patients. Early identification of patients at risk for severe disease is crucial for optimizing care, accurately informing patients and their families, guiding therapeutic interventions, and improving patient flow in the ED. Given that immunosuppressive drugs significantly impact lymphocyte profiles, we aimed to determine the association between prior use of immunosuppressive drugs, lymphocyte subsets, and COVID-19 severity in our population with a high prevalence of immunosuppression.

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Background: Netherton syndrome (NS) is a rare, severe genetic skin disorder, currently classified as an inborn error of immunity (IEI) due to previously reported immune dysregulation. We recently reported the results of an immunological evaluation showing no evidence for a relevant B- and/or T-cell mediated immunodeficiency, but immune responses after vaccination were not evaluated in that study. Therefore, we evaluated immune responses to three vaccine platforms in adult NS patients to further investigate the presence of a clinically relevant B- and/or T-cell immunodeficiency.

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Background: For the selective detection of thyroid-stimulating hormone receptor antibodies with stimulating properties (thyroid-stimulating immunoglobulins; TSI), a novel and rapid bioassay (Turbo TSI) has been introduced. We evaluate the clinical performance of Turbo TSI in Graves' orbitopathy (GO) patients and compare it to a bridge-based TSI binding immunoassay and third generation TSH-R-binding inhibitory immunoglobulins (TBII) assay. Also, we investigate the association of Turbo TSI and TBII measurements with GO activity and severity, as well as response to intravenous methylprednisolone (IVMP), and compare results to previous findings on the bridge-based TSI binding immunoassay.

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  • Granulomatous disease can occur in up to 20% of patients with Common Variable Immunodeficiency (CVID), with granulomas forming in response to unknown antigenic triggers.
  • This study aimed to compare the cellular organization and protein expression of CVID granulomas with those in other granulomatous diseases like sarcoidosis and tuberculosis.
  • Findings showed that CVID granulomas are smaller and have distinct cellular characteristics, including a higher presence of certain immune cells, indicating a different underlying cause for their formation compared to other granulomatous diseases.
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  • This study investigated serum levels and activity of interferon (IFN) in patients with sarcoidosis and tuberculosis (TB), focusing on those with uveitis, to understand IFN's role in these diseases.
  • Serum samples from patients in Indonesia (TB) and the Netherlands (sarcoidosis) were analyzed using specific assays to measure IFN types and activity, as well as the presence of autoantibodies against IFN.
  • The results showed significantly higher levels of IFNα2 and IFNγ in sarcoidosis patients compared to TB patients, particularly in those with uveitis, suggesting that IFN may be a useful marker for distinguishing between these two similar conditions.
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The appearance of brain metastasis is the most serious complication of breast cancer with mostly fatal outcomes. To reach the brain, tumor cells need to pass the blood-brain barrier (BBB). The molecular mechanisms underlying penetration of the BBB are largely unknown.

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  • Sarcoidosis and tuberculosis (TB) are similar granulomatous diseases that can cause uveitis, prompting a study of inflammation-related proteins in serum from patients in the Netherlands (sarcoidosis) and Indonesia (TB).
  • Researchers found 192 proteins unique to sarcoidosis and 102 unique to active pulmonary TB when compared to healthy controls, but noted overlapping immune pathways in both diseases.
  • A specific B-lymphocyte activation signature linked to sarcoidosis was identified, distinguishing it from TB, indicating that B-cell signaling differences are a crucial immunological factor between the two conditions.
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  • STAT3 gain-of-function variants lead to a complex clinical condition with symptoms like early immunodeficiency, autoimmunity, and lymphoproliferation, though individual variant effects are not fully understood.
  • Researchers created a mouse model based on a specific STAT3 variant from a family with common and rare symptoms, revealing increased STAT3 activity and associated health issues like splenomegaly and lymphadenopathy.
  • The study highlights the importance of variant-specific effects in understanding STAT3-associated diseases and suggests that these mouse models could help in developing personalized treatments.
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Introduction: There is a scarcity of long-term follow-up data and management strategies for recurrent uveitis in tubercular uveitis (TBU), especially in cases extending beyond 10 years after the completion of initial antitubercular treatment (ATT).

Methods: This retrospective study involved five TBU patients who were initially treated with a combination of four-drug ATT for 6 months, and the five of them had more than 10 years of follow-up after uveitis resolution upon ATT completion. We describe the occurrence of recurrent uveitis and present our approach to managing these recurrent episodes.

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Introduction: Sarcoidosis is a multi-system inflammatory disease of unknown origin with heterogeneous clinical manifestations varying from a single organ non-caseating granuloma site to chronic systemic inflammation and fibrosis. Gene expression studies have suggested several genes and pathways implicated in the pathogenesis of sarcoidosis, however, due to differences in study design and variable statistical approaches, results were frequently not reproducible or concordant. Therefore, meta-analysis of sarcoidosis gene-expression datasets is of great importance to robustly establish differentially expressed genes and signalling pathways.

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Purpose: To assess the clinical relevance of pathophysiology-based biomarkers, specifically serum C1q and whole blood interferon gene signature score (IGSS), in ocular tuberculosis (OTB) diagnosis by conducting an integrative analysis of clinical presentations and treatment response.

Methods: This retrospective cohort study analysed data from 70 patients with suspected OTB at a tertiary care uveitis practice in Indonesia. Serum C1q levels and whole blood IGSS were quantified.

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Article Synopsis
  • The study compares ocular tuberculosis (OTB) patients in the Netherlands, a low TB-endemic country, with those in Indonesia, a high TB-endemic country, focusing on clinical features, treatment approaches, and outcomes.
  • Indonesian patients exhibited more severe symptoms and complications, such as higher rates of blindness and acute uveitis, while both groups had similar overall treatment success rates.
  • Key predictors of poor treatment response included the presence of severe anterior chamber cells, specific types of eye lesions, and retinal vasculitis at the start of treatment.
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Signal Transducer and Activator of Transcription (STAT) proteins play pivotal roles in immune regulation. The dysregulation of these proteins, attributed to both gain-of-function (GOF) and loss-of-function (LOF) variants, has emerged as a substantial and intricate area of research. This comprehensive review delves into the intricate details of the diverse clinical spectrum associated with STAT variants and the immunological findings linked to these genetic alterations.

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Aims: To assess the risk of uveitis relapse in ocular tuberculosis (OTB) following clinical inactivity, to analyse clinical factors associated with relapses and to describe the management strategies for relapses.

Methods: A retrospective study was conducted on a 10-year patient registry of patients with OTB diagnosed at Erasmus MC in Rotterdam, The Netherlands. Time-to-relapse of uveitis was evaluated with Kaplan-Meier curve and risk factors for relapses were analysed.

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Background: Thyroid stimulating immunoglobulins (TSI) play a central role in the pathogenesis of Graves' orbitopathy (GO), while soluble interleukin-2 receptor (sIL-2R) is a marker for T-cell activity. We investigated TSI and sIL-2R levels in relation to thyroid function, disease activity and severity and response to treatment with intravenous methylprednisolone (IVMP) in patients with GO.

Methods: TSI (bridge-based TSI binding assay), sIL-2R, TSH and fT4 levels were measured in biobank serum samples from 111 GO patients (37 male, 74 female; mean age 49.

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Graves' ophthalmopathy (GO) is an extra-thyroidal complication of Graves' disease which can lead to vision loss in severe cases. Currently, treatments of GO are not sufficiently effective, so novel therapeutic strategies are needed. As platelet-derived growth factor (PDGF)-BB induces several effector mechanisms in GO orbital fibroblasts including cytokine production and myofibroblast activation, this study aims to investigate the roles of histone lysine methyltransferases (HKMTs) in PDGF-BB-activated GO orbital fibroblasts by screening with HKMTs inhibitors library.

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The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers).

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Article Synopsis
  • Long-term levels of glucocorticoids, specifically cortisol and cortisone measured in hair samples, indicate cumulative exposure and have shown links to various health parameters.
  • This study analyzed 6,341 hair samples from participants over a 5 to 7 year period to assess the relationship between hair glucocorticoid levels and the incidence of cardiovascular diseases (CVD).
  • The results indicated that higher hair cortisone levels are significantly associated with an increased risk of developing CVD, especially in younger individuals, suggesting that monitoring these levels could help identify those at risk and inform preventative treatments.
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Objectives: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients.

Methods: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation.

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Introduction: Perioperative music can have beneficial effects on postoperative pain, anxiety, opioid requirement, and the physiological stress response to surgery. The aim was to assess the effects of intraoperative music during general anesthesia in patients undergoing surgery for esophagogastric cancer.

Materials And Methods: The IMPROMPTU study was a double-blind, placebo-controlled, randomized multicenter trial.

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Background: Graves' disease (GD) is caused by the production of TSH-receptor (TSHR) stimulating auto-antibodies. Over the years various TSHR-antibody (TRAb) detection assays have been developed. Most clinical laboratories use competitive TSH-binding inhibitory immunoglobulin (TBII) assays, which measure the total amount of stimulating and blocking auto-antibodies.

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Background: Many patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs).

Methods: Long COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge.

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Background: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C.

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