- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Metabolomics and Mass Spectrometry Studies
- Psoriasis: Treatment and Pathogenesis
- Immunotherapy and Immune Responses
- Dermatology and Skin Diseases
- Diabetes and associated disorders
- Renal Transplantation Outcomes and Treatments
- CAR-T cell therapy research
- Immune responses and vaccinations
- Immunodeficiency and Autoimmune Disorders
- HIV Research and Treatment
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- Vitamin D Research Studies
- Cancer Immunotherapy and Biomarkers
- Cytomegalovirus and herpesvirus research
- Single-cell and spatial transcriptomics
- Wound Healing and Treatments
- Systemic Sclerosis and Related Diseases
- Burn Injury Management and Outcomes
- Long-Term Effects of COVID-19
- HIV-related health complications and treatments
- SARS-CoV-2 and COVID-19 Research
- Cytokine Signaling Pathways and Interactions
Radboud University Nijmegen
2016-2025
Radboud University Medical Center
2016-2025
University Medical Center
2016-2023
Radboud Institute for Molecular Life Sciences
2013-2021
Laboratory of Molecular Genetics
2011-2016
State Key Laboratory of Medical Immunology
2014
Nijmegen Institute for Scientist Practitioners in Addiction
2010-2013
Institute of Infection and Immunity
2011
National Blood Transfusion Service
2006
Dutch Blood Transfusion Society
1998
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the immunity is associated with bias toward granulopoiesis bone marrow hematopoietic progenitor but it unknown whether BCG vaccination also leads to functional reprogramming mature neutrophils. Here, we show healthy...
Effective immunity requires a complex network of cellular and humoral components that interact with each other are influenced by different environmental host factors. We used systems biology approach to comprehensively assess the impact genetic factors on immune cell populations in peripheral blood, including associations immunoglobulin concentrations, from ∼500 healthy volunteers Human Functional Genomics Project. Genetic heritability estimation showed variations T numbers more strongly...
Regulatory T cell (Treg)-mediated immunosuppression is considered a major obstacle for successful cancer immunotherapy. The association between clinical outcome and Tregs being studied extensively in trials, but unfortunately, no consensus has been reached about (a) the markers (b) gating strategy required to define human this context, making it difficult draw final conclusions. Therefore, we have organized an international workshop on detection functional testing of with leading experts...
Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate activation and memory that indicative immunity. We established personal profiles chromatin accessibility maps over a 90-day time course BCG vaccination in 323 Our...
A single dose of the anti-CD20 monoclonal antibody rituximab induces a nearly complete B cell depletion in peripheral blood, but not secondary lymphoid organs. Modulation this remaining population due to treatment may contribute therapeutic effects rituximab. To assess vivo we used lymph nodes (LNs) collected during renal transplant surgery patients who had received 4 weeks earlier preparation for an ABO-incompatible transplantation. Rituximab resulted lower percentage naïve (IgD(+)CD27(-))...
The immune modulating capacity of vitamin D(3) is well-recognized. Ultra-violet (UV) exposure determines production in vivo and varies through the course year, especially temperate regions. However, it not known whether human innate response differs due to seasonality. To validate seasonal effects , effect 1,25(OH)(2) on peripheral blood mononuclear cells (PBMC) cytokine was first determined vitro. decreased interleukin (IL)-6 tumour necrosis factor (TNF)-α release by PBMC stimulated with...
Abstract The V-ATPase is the main regulator of intra-organellar acidification. Assembly this complex has extensively been studied in yeast, while limited knowledge exists for man. We identified 11 male patients with hemizygous missense mutations ATP6AP1 , encoding accessory protein Ac45 V-ATPase. Homology detection at level sequence profiles indicated as long-sought human homologue yeast assembly factor Voa1. Processed wild-type Ac45, but not its disease mutants, restored V-ATPase-dependent...
We evaluated the efficacy and safety of rituximab as induction therapy in renal transplant patients. In a double-blind, placebo-controlled study, 280 adult patients were randomized between single dose (375 mg/m(2)) or placebo during surgery. Patients stratified according to panel-reactive antibody (PRA) value rank number transplantation. Maintenance immunosuppression consisted tacrolimus, mycophenolate mofetil steroids. The primary endpoint was incidence biopsy proven acute rejection (BPAR)...
Abstract The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. disease severity correlates with an excessive proinflammatory immune profound lymphopenia. Inflammatory responses according to were explored by plasma cytokine measurements proteomics analysis 147 patients. Furthermore, peripheral blood mononuclear cell production assays whole flow cytometry performed. Results confirm a hyperinflammatory innate...
Severe burn injury causes local and systemic immune responses that can persist up to months, lead inflammatory response syndrome, organ damage long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed temporal peripheral blood profile 20 wound patients admitted intensive care by flow cytometry secretome profiling, compared data from healthy subjects. The...
Treg based immunotherapy is of great interest to facilitate tolerance in autoimmunity and transplantation. For clinical trials, it essential have a grade isolation protocol accordance with Good Manufacturing Practice (GMP) guidelines. To obtain sufficient for immunotherapy, subsequent ex vivo expansion might be needed.Treg were isolated from leukapheresis products by CliniMACS GMP strategies, using anti-CD25, anti-CD8 anti-CD19 coated microbeads. procedures led 40-60% pure...
Mycophenolic acid is the active ingredient of immunosuppressant mycophenolate mofetil that widely used in transplantation medicine and autoimmunity. inhibits inosine monophosphate dehydrogenase, an enzyme involved biosynthesis guanine nucleotides required for lymphocyte clonal expansion. Here, we present novel insights into mechanisms underlying mycophenolic acid-mediated suppression human CD4+ T cells. Upon CD3/CD28 stimulation, inhibited cell IL-17, IFN-γ TNF-α production but not IL-2...