A5065346015- Renal Transplantation Outcomes and Treatments
- Renal Diseases and Glomerulopathies
- Organ Transplantation Techniques and Outcomes
- T-cell and B-cell Immunology
- Complement system in diseases
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Transplantation: Methods and Outcomes
- Cytomegalovirus and herpesvirus research
- Organ and Tissue Transplantation Research
- Hematopoietic Stem Cell Transplantation
- Cancer Immunotherapy and Biomarkers
- Diabetes and associated disorders
- Acute Lymphoblastic Leukemia research
- Medical Imaging and Pathology Studies
- Pregnancy and Medication Impact
- Autoimmune and Inflammatory Disorders Research
- Advanced biosensing and bioanalysis techniques
- Liver Disease and Transplantation
- Inflammatory Bowel Disease
- Polyomavirus and related diseases
- Viral Infections and Immunology Research
- Psoriasis: Treatment and Pathogenesis
- Systemic Lupus Erythematosus Research
- Dermatology and Skin Diseases
University Medical Center Utrecht
2016-2024
Utrecht University
2018-2021
University Medical Center
2018
Radboud University Medical Center
2011-2015
Radboud University Nijmegen
2010-2015
Radboud Institute for Molecular Life Sciences
2013
Nijmegen Institute for Scientist Practitioners in Addiction
2013
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(-))...
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)...
Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for reliable tool to define permissible in We previously demonstrated that donor-derived Predicted Indirectly ReCognizable Epitopes presented by recipient class II (PIRCHE-II) play role de novo DSA formation In the present Dutch multi-center study we evaluated possible association between PIRCHE-II and failure 2,918 donor-recipient couples were transplanted 1995 2005....
The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, II, or both classes indicate a different for loss between deceased and living donor In this study, we investigated the impact pretransplant DSAs, by using single antigen bead assays, on long-term survival in 3237 1487 transplants negative complement-dependent crossmatch. transplants, found limited effect I II...
The clinical significance of non-HLA antibodies on renal allograft survival is a matter debate, due to differences in reported results and lack large-scale studies incorporating analysis multiple simultaneously. We developed multiplex antibody assay against 14 proteins highly expressed the kidney. In this study, presence pretransplant was correlated nationwide cohort 4770 recipients transplanted between 1995 2006. Autoantibodies Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly...
Prevention of rejection after renal transplantation requires treatment with immunosuppressive drugs. Data on their in vivo effects T- and B-cell phenotype function are limited.In a randomized double-blind placebo-controlled study to prevent allograft rejection, patients were treated tacrolimus, mycophenolate mofetil (MMF), steroids, single dose rituximab or placebo during transplant surgery. In subset patients, we analyzed the number peripheral T B cells by multiparameter flow cytometry...
Background. The impact of donor-specific anti-HLA antibodies (DSA) on antibody-mediated rejection (AMR) and kidney allograft failure is well established. However, the relevance non-HLA remains unclear. Methods. We investigated 13 pretransplant their association with histology AMR (AMR h ) failure. included single recipients (n = 203) , according to Banff 2017 classification matched -free controls 219). Non-HLA were assessed using multiplex Luminex assay. Results. Of selected (against agrin,...
Cardiac allograft vasculopathy (CAV) is a transplant pathology, limiting graft survival after heart transplantation. CAV arteries are surrounded by ectopic lymphoid structures (ELS) containing B cells and plasma cells. The aim of this study was to characterize the antigenic targets antibodies produced in ELS. Coronary surrounding epicardial tissue from 56 recipients were collected during autopsy. Immunofluorescence used identify antibody-producing Immunoglobulin levels lysates measured...
Background. There is no consensus in the literature on interpretation of single-antigen bead positive for a specific HLA antibody. Methods. To inform debate, we studied relationship between various positivity algorithms and impact resulting donor-specific antibody (DSA) long-term kidney graft survival 3237 deceased-donor transplants. Results. First, showed that interassay variability can be greatly reduced when working with signal-to-background ratios instead absolute median fluorescence...
The best treatment for patients with end-stage renal disease is kidney transplantation. Although graft survival rates have improved in the last decades, still may lose their grafts partly due to detrimental effects of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) and a lesser extent also by directed non-HLA expressed on donor endothelium. Assays detect anti-HLA are already use many years been proven useful transplant risk stratification. Currently, there need assays...
Rituximab is a chimeric anti-CD20 monoclonal antibody (mAb) used in B-cell malignancies, various autoimmune disorders and organ transplantation. Although administration of single dose rituximab results full depletion peripheral blood, there remains residual population secondary lymphoid organs. These nondepleted B cells might be altered by exposure to with subsequent immunomodulatory effects. Therefore, we analyzed vitro the effects on proliferation, activation differentiation CD19(+) means...
Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection anti-HLA that bind C3d. Because early humoral graft rejection is to be complement mediated, this SAB-based technique may provide valuable tool in pretransplant risk stratification transplant recipients. Methods Previously, we established donor-specific (DSAs) associated with increased long-term failure...
Pre-transplant donor-specific anti–human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA (nDSAs) is more controversial. The aim present paired study was to compare DSAs and nDSAs. To eliminate donor era-dependent factors, a post hoc analysis performed as part Dutch multicentre evaluating all transplantations between 1995 2005 available pre-transplant serum samples. Anti-HLA were detected...
CD4 + T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well cellular responses, which might lead to failure of the allograft. memory from a previous immunizing event can potentially be reactivated exposure HLA mismatches that share T-cell epitopes with initial HLA. Consequently, reactivity toward are shared between and donor could increase risk alloimmunity transplantation, thus affecting transplant outcome. In this study,...
Abstract Solid‐phase multiplex‐bead assays are widely used in transplantation to detect anti‐human leukocyte antigen ( HLA ) antibodies. These enable high resolution detection of low levels However, costly and yield variable measurements that limit the comparison results between laboratories. In context a Dutch national Consortium study we aimed determine inter‐assay inter‐machine variability assays, assessed how reduce assay reagents costs. Fifteen sera containing variety antibodies were...
Treatment with rituximab may be accompanied by a systemic cytokine release. We studied the effects of single dose on levels in transplant patients and examined underlying mechanism.Twenty renal recipients (10 rituximab-treated, 10 placebo-treated) were recruited from randomized clinical trial. Rituximab or placebo was infused during surgery, blood samples taken before, during, after surgery analyzed for interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, interferon-γ, macrophage...
Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based historical data, it was not possible to account for presence pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker impaired graft survival. The aim this study evaluate what extent frequently used initial therapies increase survival in immunological low-risk patients.We performed an...
INTRODUCTION AND AIMS: Pretransplant donor-specific anti-HLA antibodies (DSA) are associated with impaired kidney graft survival.Some studies showed that non-donor specific (nDSA) also an important risk marker for loss, whereas others did only find a limited effect.Donor factors and era-dependent changes may interfere these analyses.To eliminate factors, we have performed post-hoc paired analysis on Dutch multicenter study evaluating all transplantations between 1995-2005 available...
Event Abstract Back to A single dose of rituximab does not deplete B cells in secondary lymphoid organs, but alters phenotype and function Elena Kamburova1*, Hans J. Koenen1, Kyra Borgman1, Ineke Ten Berge2, Irma Joosten1 Luuk Hilbrands1 1 Radboud University Medical Centre Nijmegen, Netherlands 2 Academic Centre, the anti-CD20 monoclonal antibody induces a nearly complete B-cell depletion peripheral blood, organs. Modulation this remaining population due treatment may contribute therapeutic...