5 results on '"Wenink, Mark H."'
Search Results
2. Impaired Porphyromonas gingivalis-Induced Tumor Necrosis Factor Production by Dendritic Cells Typifies Patients With Rheumatoid Arthritis.
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Santegoets, Kim C. M., Wenink, Mark H., Braga, Felipe A. Vieira, Cossu, Marta, Lamers‐Karnebeek, Femke B. G., van Riel, Piet L. C. M., Sturm, Patrick D. J., van den Berg, Wim B., and Radstake, Timothy R. D. J.
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ACADEMIC medical centers , *CELL culture , *CHRONIC diseases , *DENDRITIC cells , *FLOW cytometry , *PERIODONTITIS , *POLYMERASE chain reaction , *RESEARCH funding , *RHEUMATOID arthritis , *T-test (Statistics) , *TUMOR necrosis factors , *DESCRIPTIVE statistics , *GRAM-negative anaerobic bacteria , *MANN Whitney U Test - Abstract
Objective The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA), and the severity of periodontitis can affect the level of arthritis. Porphyromonas gingivalis is one of the main bacteria involved in periodontitis. Our aim was to determine if there are differences in the innate immune response against P gingivalis between healthy controls and RA patients. Methods Monocyte-derived dendritic cells (DCs) from healthy controls, RA patients, and patients with psoriatic arthritis (PsA) were stimulated with P gingivalis, a range of other bacteria, and Toll-like receptor agonists. Cytokine production was determined, and blocking studies were performed to determine which receptors were involved in differential recognition of P gingivalis. Effects on T cell cytokines were also determined in cultures of peripheral blood mononuclear cells (PBMCs). Results Upon stimulation with P gingivalis, RA patient DCs produced less tumor necrosis factor as compared to healthy control DCs, which was not observed in PsA patients or upon stimulation with other bacteria. In addition, P gingivalis-mediated activation of RA patient PBMCs showed a clear reduction of interferon-γ production. Among the various possible underlying mechanisms investigated, only blockade of CR3 abolished the difference between RA patients and healthy controls, suggesting the involvement of CR3 in this process. Conclusion Immune cells from RA patients display a reduced response to P gingivalis, which has functional consequences for the immune response. This may result in prolonged survival of P gingivalis, possibly driving autoantibody formation and a self-perpetuating loop of chronic inflammation. The possible role of CR3 in this process warrants further investigation. [ABSTRACT FROM AUTHOR]
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- 2016
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3. Fc Gamma Receptor IIb on GM-CSF Macrophages Controls Immune Complex Mediated Inhibition of Inflammatory Signals.
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Santegoets, Kim C. M., Wenink, Mark H., van den Berg, Wim B., and Radstake, Timothy R. D. J.
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RHEUMATOID arthritis , *MACROPHAGES , *TOLL-like receptors , *T cells , *LIGANDS (Biochemistry) , *MACROPHAGE activation , *CYTOKINES - Abstract
Background: In rheumatoid arthritis (RA) macrophages play a major role in amplifying synovial inflammation. Important activating signals are those induced by Toll-like receptor (TLR) ligands and by activated T cells. The balance between activating and inhibitory Fc gamma receptors (FcγRs) on macrophages might be crucial in modulating these inflammatory responses. The purpose of this study was to determine FcγR expression on pro- and anti-inflammatory macrophages (gmMφ and mMφ, respectively) and identify functional consequences on immune complex uptake and macrophage activation. Methods: Human monocytes were isolated and differentiated into gmMφ and mMφ. A full FcγR characterization of both macrophage subtypes was performed and uptake of fluorescent immune complexes (ICs) was determined. FcγRIIb isoforms were determined by qPCR. Macrophages were stimulated via different TLRs or cytokine activated T cells in the presence or absence of ICs and cytokine production was determined. Blocking studies were performed to look into the pathways involved. Results: mMφ expressed high levels of the activating FcγRIIa and FcγRIII and low levels of the inhibitory FcγRIIb, while the FcγR balance on gmMφ was shifted towards the inhibitory FcγRIIb. This was accompanied by a clear increase in FcγRIIb1 mRNA expression in gmMφ. This resulted in higher IC uptake by mMφ compared to gmMφ. Furthermore, FcγR-mediated stimulation of gmMφ inhibited TLR2, 3, 4 and 7/8 mediated cytokine production via FcγRIIb and PI3K signaling. In addition, gmMφ but not mMφ produced TNFα upon co-culture with cytokine activated T cells, which was reduced by IC binding to FcγRIIb. The latter was dependent on PI3K signaling and COX2. Conclusions: FcγR expression patterns on gmMφ and mMφ are significantly different, which translates in clear functional differences further substantiating FcγRIIb as an interesting target for inflammation control in RA and other autoimmune/inflammatory diseases. [ABSTRACT FROM AUTHOR]
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- 2014
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4. Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial.
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Michielsens, Celia A. J., Boers, Nadine, den Broeder, Nathan, Wenink, Mark H., van der Maas, Aatke, Mahler, Elien A. M., Mulder, Michelle L. M., van der Heijde, Désirée, van den Hoogen, Frank H. J., Verhoef, Lise M., and den Broeder, Alfons A.
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PSORIATIC arthritis , *LABELS , *RHEUMATOID arthritis , *BAYESIAN analysis , *THERAPEUTICS , *DRUG side effects - Abstract
Background: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies.Methods: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total.Discussion: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences.Trial Registration: Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018). [ABSTRACT FROM AUTHOR]- Published
- 2020
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5. Preferences of patients with rheumatoid arthritis regarding disease-modifying antirheumatic drugs: a discrete choice experiment.
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Heuckelum, Milou van, Mathijssen, Elke GE, Vervloet, Marcia, Boonen, Annelies, Hebing, Renske CF, Pasma, Annelieke, Vonkeman, Harald E, Wenink, Mark H, Bemt, Bart JF van den, and Dijk, Liset van
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MEDICAL personnel , *RHEUMATOID arthritis , *CONSUMER preferences , *LOGISTIC regression analysis - Abstract
Background: Although patients have different treatment preferences, these individual preferences could often be grouped in subgroups with shared preferences. Knowledge of these subgroups as well as factors associated with subgroup membership supports health care professionals in the understanding of what matters to patients in clinical decision-making. Objectives: To identify subgroups of patients with rheumatoid arthritis (RA) based on their shared preferences toward disease-modifying antirheumatic drugs (DMARDs), and to identify factors associated with subgroup membership. Methods: A discrete choice experiment to determine DMARD preferences of adult patients with RA was designed based on a literature review, expert recommendations, and focus groups. In this multicenter study, patients were asked to state their preferred choice between two different hypothetical treatment options, described by seven DMARD characteristics with three levels within each characteristic. Latent class analyses and multinomial logistic regressions were used to identify subgroups and the characteristics (patient characteristics, disease-related variables, and beliefs about medicines) associated with subgroup membership. Results: Among 325 participating patients with RA, three subgroups were identified: an administration-driven subgroup (45.6%), a benefit-driven subgroup (29.7%), and a balanced subgroup (24.7%). Patients who were currently using biologic DMARDs were significantly more likely to belong to the balanced subgroup than the administration-driven subgroup (relative risk ratio (RRR): 0.50, 95% CI: 0.28–0.89). Highly educated patients were significantly more likely to belong to the benefit-driven subgroup than the balanced subgroup (RRR: 11.4, 95% CI: 0.97–133.6). Patients' medication-related concerns did not contribute significantly to subgroup membership, whereas a near-significant association was found between patients' beliefs about medication necessity and their membership of the benefit-driven subgroup (RRR: 1.12, 95% CI: 1.00–1.23). Conclusion: Three subgroups with shared preferences were identified. Only biologic DMARD use and educational level were associated with subgroup membership. Integrating patient's medication preferences in pharmacotherapy decisions may improve the quality of decisions and possibly medication adherence. [ABSTRACT FROM AUTHOR]
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- 2019
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