Transplantation Immunology Group

Risk stratification

Identification of new biomarkers and the use of prediction models can ensure early detection of graft deterioration. In our laboratory, several biomarkers have been developed such as dd-cfDNA, extracellular vesicles, and chemokines. Additionally, biomarkers of organ quality during machine perfusion are being studied in context of the Flagship Organ Transplantation within Convergence. We use AI to develop prediction models for the stratification of individual patients’ risk for rejection and graft loss, based on demographic, immunological, clinical, histological and pharmacological parameters, in collaboration with the Department of Pathology and Clinical Bioinformatics. The goal of prediction models is to enable personalized therapy and maximize graft survival.

Improved HLA matching

Currently, HLA matching for kidney transplantation is done at the antigen level with essentially each mismatch weighing equally. However, not every HLA mismatch is equivalent in degree of immunological risk. It is possible to perform HLA matching with much greater precision at the molecular level (epitopes). Reduction of HLA epitope mismatches may contribute to reduced immunological risk. Additionally, based on epitope mismatch levels, the dosing of immunosuppressive medication can likely be personalized. We study the immunogenicity of epitope mismatches, applying epitope analysis software HLA-EMMA in clinical studies, and studying HLA epitope – antibody paratope interactions, in collaboration with the HLA diagnostics laboratory at the LUMC.

Novel therapies

Current therapies to reduce HLA sensitization, and to prevent or treat graft rejection, are non-specific and result in suppression of the entire immune system. Consequently, transplant patients are at increased risk for infections and malignancies. There is a clear demand for personalized therapies that specifically target alloimmune responses, without compromising protective defenses. Recently, we have developed a new potential therapy to treat HLA sensitization and antibody-mediated rejection using Chimeric HLA Antigen Receptor (CHAR) T cells. CHAR T cells can selectively eliminate HLA-specific B cells, without attacking B cells with other specificities. This research is conducted in collaboration with the Department of Hematology of the LUMC.

Immunologically 'invisible' organs

An alternative way to extend the lifespan of transplanted organs is to remove or dampen the initial immunological 'trigger' in order to make them immunologically invisible to the immune system. This may be possible by (temporarily) disabling the expression of red blood group AB glycans, and/or HLA molecules on the graft, combined with induction of immune regulatory molecules, which are necessary to inhibit specific immune cells. Together with the Kidney Organoid group in our lab we work on organoid models where we use genetic modification to minimize immunogenicity. We use several types of immune cells and mediators to study the immunogenicity of the modified cells.

• Developing novel biomarkers for post-transplantation outcomes, as well as organ quality during machine perfusion
• Studying immune responses against respiratory viruses in kidney transplant recipients
• Using computer simulations to study the impact of changes in living donor kidney exchange transplantation, including epitope mismatches
• Further developing Chimeric HLA Antigen Receptor T cell therapy
• Exploring of and interfering with allo-immune responses in a kidney organoid model

Collaboration within Erasmus MC

• Dr. H. de Jong, Department of Paediatric Nephrology
• Dr. A. Stubbs, Department of Pathology and Clinical Bioinformatics
• Dr. J. Demmers, Department of Biochemistry
• Dr. S.I. Buschow, Department of Gastroenterology & Hepatology

Collaboration outside of Erasmus MC

• Prof. Dr. M.H.M. Heemskerk, Department of Hematology, LUMC, Leiden, the Netherlands
• Dr. D.L. Roelen, Department of Immunology, LUMC, Leiden, the Netherlands
• Prof. Dr. F. Diekmann, Department of Nephrology and Kidney Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain
• Prof. Dr. L. West, Departments of Pediatrics, Surgery, and Immunology, University of Alberta, Canada

• Kidney Organoid Group
• Sebastiaan Heidt, PhD, associate professor
• Carla Baan, PhD, professor
• Karin Boer, PhD, assistant professor
• Nicolle Litjens, PhD, assistant professor
• Hector Tejeda Mora, PhD
• Alvaro Assis de Souza, Msc, PhD candidate
• Britte Lenderink, Msc, PhD candidate
• Hannah Schenk, Msc, PhD candidate
• Karim Bousnina, Msc, PhD candidate
• Liang Wu, PhD candidate
• Yvette den Hartog, PhD candidate
• Annemiek Peeters, technician
• Derek Reijerkerk, technician
• Mariska Klepper, technician
• Marjolein Marijnissen – Dieterich, technician
• Rens Kraaijveld, technician
• Ronella de Kuiper, technician
• Wenda Verschoor, technician