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Coco de Koning, Rick Admiraal, Stefan Nierkens, Jaap Jan Boelens
Unrelated umbilical cord blood transplantation (UCBT) exhibits a low risk of graft-versus-host-disease (GvHD) and has unique potent anti-virus and anti-leukemia effects. Anti-thymocyte globulin (ATG) in the conditioning regimen for UCBT is successful in reducing graft rejection and GvHD. Nevertheless, this beneficial effect of ATG coincides with its detrimental effect on immune reconstitution. The latter directly relates to a high incidence of viral infections and leukemia relapses. ATG has been used in transplant patients for over 30 years...
2017: Stem Cell Investigation
Judith Lydia Thijs, Ian Strickland, Catharina Ansfrieda Francisca Maria Bruijnzeel-Koomen, Stefan Nierkens, Barbara Giovannone, Eszter Csomor, Bret Richard Sellman, Tomas Mustelin, Matthew Alexander Sleeman, Marjolein Saskia de Bruin-Weller, Athula Herath, Julia Drylewicz, Richard David May, DirkJan Hijnen
BACKGROUND: Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease with a diverse clinical presentation. It is however unclear whether this diversity exists at a biological level. OBJECTIVE: To test the hypothesis that AD is heterogeneous at the biological level of individual inflammatory mediators. METHODS: Serum from 193 moderate to severe adult AD patients (geomean (95%CI) SASSAD of 22.3 (21.3, 23.3) and 39.1 (37.5, 40...
April 12, 2017: Journal of Allergy and Clinical Immunology
Rick Admiraal, Coco de Koning, Caroline A Lindemans, Marc B Bierings, Annemarie M J Wensing, A Birgitta Versluys, Tom F W Wolfs, Stefan Nierkens, Jaap Jan Boelens
BACKGROUND: Viral reactivations (VR) following hematopoietic cell transplantation (HCT) contribute to significant morbidity and mortality. Timely immune reconstitution (IR) is suggested to prevent VR. OBJECTIVES: We studied the relation between IR (as a continuous over-time-predictor) and VR (as time-varying-predictor), and the relation between VR and other clinical outcomes. METHODS: In this retrospective analysis, all patients receiving a first HCT between January-2004 and September-2014 were included...
April 6, 2017: Journal of Allergy and Clinical Immunology
Carolijn Smids, Carmen S Horjus Talabur Horje, Stefan Nierkens, Julia Drylewicz, Marcel J M Groenen, Peter J Wahab, Ellen G van Lochem
Background and Aim: More than half of patients with Crohn's disease (CD) develop disease complications requiring aggressive medical therapy or surgery over time. However, predicting disease course and treatment response remains difficult. We therefore identified distinctive serum analytes associated with disease activity and course in newly diagnosed, untreated patients at presentation and during their follow-up. Methods: In a pilot study, a multiplex immunoassay analysis on 36 markers was performed on serum from 20 CD patients at the time of primary diagnosis following endoscopic evaluation...
March 27, 2017: Journal of Crohn's & Colitis
Rick Admiraal, Stefan Nierkens, Moniek A de Witte, Eefke J Petersen, Ger-Jan Fleurke, Luka Verrest, Svetlana V Belitser, Robbert G M Bredius, Reinier A P Raymakers, Catherijne A J Knibbe, Monique C Minnema, Charlotte van Kesteren, Jurgen Kuball, Jaap J Boelens
BACKGROUND: Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation between exposure to ATG and clinical outcomes in adult patients with acute leukaemia and myelodysplastic syndrome. METHODS: We did a retrospective, pharmacokinetic-pharmacodynamic analysis of data from patients with acute lymphoid leukaemia, acute myeloid leukaemia, or myelodysplastic syndrome receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT with ATG (thymoglobulin) as part of non-myeloablative conditioning from March 1, 2004, to June 1, 2015...
April 2017: Lancet Haematology
C Smids, C Horjus Talabur Horje, S Nierkens, J Drylewicz, M Groenen, P Wahab, E van Lochem
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
J J W Kuiper, L Beretta, S Nierkens, R van Leeuwen, N H Ten Dam-van Loon, J Ossewaarde-van Norel, M C Bartels, J D F de Groot-Mijnes, P Schellekens, J H de Boer, T R D J Radstake
Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test...
January 27, 2017: Scientific Reports
Roos-Marijn Berbers, Stefan Nierkens, Jacob M van Laar, Debby Bogaert, Helen L Leavis
Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID...
March 2017: Trends in Immunology
Narges Seyfizadeh, Ravikumar Muthuswamy, Duane A Mitchell, Stefan Nierkens, Nayer Seyfizadeh
Better prognoses associated with increased T cell infiltration of tumors, as seen with chimeric antigen receptor (CAR) T cell therapies and immune checkpoint inhibitors, portray the importance and potential of the immune system in controlling tumors. This has rejuvenated the field of cancer immunotherapy leading to an increasing number of immunotherapies developed for cancer patients. Dendritic Cells (DCs) vaccines represent an appealing option for cancer immunotherapy since DCs have the ability to circumvent tolerance to tumors by its adjuvant properties and to induce memory T cells that can become persistent after initial tumor clearance to engage potential metastatic tumors...
November 2016: Critical Reviews in Oncology/hematology
Lonneke M JanssenDuijghuijsen, Jaap Keijer, Marco Mensink, Kaatje Lenaerts, Lars Ridder, Stefan Nierkens, Shirley W Kartaram, Martie C M Verschuren, Raymond H H Pieters, Richard Bas, Renger F Witkamp, Harry J Wichers, Klaske van Norren
What is the central question of this study? Exercise is known to induce stress-related physiological responses, such as changes in intestinal barrier function. Our aim was to determine the test-retest repeatability of these responses in well-trained individuals. What is the main finding and its importance? Responses to strenuous exercise, as indicated by stress-related markers such as intestinal integrity markers and myokines, showed high test-retest variation. Even in well-trained young men an adapted response is seen after a single repetition after 1 week...
January 1, 2017: Experimental Physiology
Rick Admiraal, Caroline A Lindemans, Charlotte van Kesteren, Marc B Bierings, A Birgitta Versluijs, Stefan Nierkens, Jaap Jan Boelens
Successful immune reconstitution (IR) is associated with improved outcomes following pediatric cord blood transplantation (CBT). Usage and timing of anti-thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus-host disease and graft failure, negatively influences T-cell IR. We studied the relationships among ATG exposure, IR, and clinical outcomes. All pediatric patients receiving a first CBT between 2004 and 2015 at the University Medical Center Utrecht were included. ATG-exposure measures were determined with a validated pharmacokinetics model...
December 8, 2016: Blood
Coco de Koning, Stefan Nierkens, Jaap Jan Boelens
T-cell immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (allo-HCT) is highly variable between patients and may take several months to even years. Patients with delayed or unbalanced T-cell IR have a higher probability of developing transplantation-related morbidity, mortality, and relapse of disease. Hence, there is a need for strategies to better predict and improve IR to reduce these limitations of allo-HCT. In this review, we provide an update of current and in-near-future clinically relevant strategies before, during, and after transplantation to achieve successful T-cell IR...
December 8, 2016: Blood
Fleurieke Verhagen, Jonas Kuiper, Stefan Nierkens, Saskia M Imhof, Timothy Radstake, Joke de Boer
BACKGROUND: In this report we describe, for the first time, the activation of the peripheral immune compartment in a patient with a CRB1 linked retinal degenerative disease, masquerading as intermediate uveitis. METHODS: To monitor the immune system during systemic immunosuppressive treatment, given for the initial diagnosis of intermediate uveitis, blood samples were taken before and during therapy, for analysis of peripheral blood mononuclear cell-subsets and circulating immune mediators...
December 2016: Expert Review of Clinical Immunology
Marta Cossu, Lenny van Bon, Stefan Nierkens, Chiara Bellocchi, Alessandro Santaniello, Harry Dolstra, Lorenzo Beretta, Timothy R D J Radstake
Immune activation is a hallmark of systemic sclerosis (SSc). However, the immunological alterations that occur in preclinical and non-fibrotic SSc and that differentiate these subjects from those with primary Raynaud's phenomenon (PRP) or healthy controls (HC) are poorly defined. We isolated CD56(+) (NK/NKT-like) cells from HC, patients with PRP, early SSc (EaSSc) and definite SSc without skin or lung fibrosis. Cytokine production upon different activating stimuli was measured via a multiplex immuno assay. Clearly discriminative patterns among the different stages of SSc were most markedly observed after TLR1/2 stimulation, with increased IL-6, TNF-α and MIP-1α/CCL3 production in definite SSc patients as compared to HC and/or PRP...
December 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Fiona E Benson, Gera E Nagelhout, Vera Nierkens, Marc C Willemsen, Karien Stronks
In 2011, the Dutch government reimbursed smoking cessation pharmacotherapy with behavioral therapy for quitting smokers. We investigate whether inequalities in the use of pharmacotherapy change and, if not, whether this is due to a relatively positive injunctive norm in lower socioeconomic status (SES) groups. A total of 75,415 participants aged ≥15 years from the Dutch Continuous Survey of Smoking Habits, 2009-2012, were considered with the following measures: SES (education/income), injunctive norm (mostly acceptable/neutral/mostly unacceptable), period (2011/all other years), and pharmacotherapy use (yes/no)...
2016: Substance Abuse: Research and Treatment
R Admiraal, R Chiesa, C A Lindemans, S Nierkens, M B Bierings, A B Versluijs, P Hiwarkar, J M Furtado Silva, P Veys, J J Boelens
No abstract text is available yet for this article.
May 9, 2016: Bone Marrow Transplantation
C Vissenberg, K Stronks, G Nijpels, P J M Uitewaal, B J C Middelkoop, M J E Kohinor, M A Hartman, V Nierkens
OBJECTIVE: There is a need for effective interventions that improve diabetes self-management (DSM) among socioeconomically deprived patients with type 2 diabetes. The group-based intervention Powerful Together with Diabetes (PTWD) aimed to increase social support for DSM and decrease social influences hindering DSM (eg, peer pressure, social norms) in patients living in deprived neighbourhoods. Through a qualitative process evaluation, this paper aims to study whether this intervention changed social support and social influences, and which elements of the intervention contributed to this...
April 13, 2016: BMJ Open
Joris M Van Montfrans, Esther A R Hartman, Kees P J Braun, Eric A M Hennekam, Elisabeth A Hak, Paul J Nederkoorn, Willeke F Westendorp, Robbert G M Bredius, Wouter J W Kollen, Elisabeth H Schölvinck, G Elizabeth Legger, Isabelle Meyts, Adrian Liston, Klaske D Lichtenbelt, Jacques C Giltay, Gijs Van Haaften, Gaby M De Vries Simons, Helen Leavis, Cornelis J G Sanders, Marc B Bierings, Stefan Nierkens, Marielle E Van Gijn
OBJECTIVE: To determine the genotype-phenotype association in patients with adenosine deaminase-2 (ADA2) deficiency due to identical homozygous R169Q mutations inCECR1 METHODS: We present a case series of nine ADA2-deficient patients with an identical homozygous R169Q mutation. Clinical and diagnostic data were collected and available MRI studies were reviewed. We performed genealogy and haplotype analyses and measured serum ADA2 activity. ADA2 activity values were correlated to clinical symptoms...
May 2016: Rheumatology
Lotte Spel, Jaap-Jan Boelens, Dirk M van der Steen, Nina J G Blokland, Max M van Noesel, Jan J Molenaar, Mirjam H M Heemskerk, Marianne Boes, Stefan Nierkens
Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20-40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for neuroblastoma treatment, these immune escape mechanisms restrain clinical results. Therefore, we aimed to improve neuroblastoma immunogenicity to further the development of antigen-specific immunotherapy against neuroblastoma...
November 3, 2015: Oncotarget
Colin de Haar, Maud Plantinga, Nina Jg Blokland, Niek P van Til, Thijs Wh Flinsenberg, Viggo F Van Tendeloo, Evelien L Smits, Louis Boon, Lotte Spel, Marianne Boes, Jaap Jan Boelens, Stefan Nierkens
The poor survival rates of refractory/relapsed acute myeloid leukemia (AML) patients after haematopoietic cell transplantation (HCT) requires the development of additional immune therapeutic strategies. As the elicitation of tumor-antigen specific cytotoxic T lymphocytes (CTLs) is associated with reduced relapses and enhanced survival, enhanced priming of these CTLs using an anti-AML vaccine may result in long-term immunity against AML. Cord blood (CB), as allogeneic HCT source, may provide a unique setting for such post-HCT vaccination, considering its enhanced graft-versus-leukemia (GvL) effects and population of highly responsive naïve T cells...
November 2015: Oncoimmunology
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