Erythropoietin and Trained Immunity in Kidney Transplantation
Final Report Abstract
The project "Erythropoietin and Trained Immunity in Kidney Transplantation" investigates the effects of erythropoietin (EPO) therapy on the immune system in patients who have undergone kidney transplantation. EPO has been approved as a medication for over 40 years to promote the formation of red blood cells. Recent studies in mouse models have shown that EPO, in addition to its effects on blood formation, also has an impact on the immune system, extending graft survival in a mice model with heart transplants. In humans, the effects of EPO on the immune system have been demonstrated in dialysis patients and patients with liver diseases. In these cases, EPO was shown to modulate the immune response by dampening it or promoting immune tolerance. Such an effect would be particularly desirable in kidney transplant patients, as it could reduce the risk of organ rejection and potentially reduce the need for immunosuppressive medication. Since kidney transplant patients often receive EPO therapy for anemia, this project examines the effects of EPO in this patient group. In this study, 34 kidney transplant patients were included, all of whom had a medical indication for starting EPO therapy (anemia), had not received EPO for at least 3 months prior, and had stable kidney transplant function. Blood and urine samples were taken twice before the start of EPO therapy (2 baseline samples) and 4 weeks after initiating EPO therapy. EPO therapy was administered once weekly. First, the effects of EPO on immune cells were tested in vitro by adding EPO to cells from healthy donors. Then, the effects of EPO on immune cells from kidney transplant patients were tested by adding EPO to immune cells of kidney transplant patients without EPO therapy in the laboratory. These experiments allowed for the investigation of the direct effect of EPO on specific immune cells and the development of a testing method using a sensor designed by our collaboration partner. Subsequently, the blood samples from the patient cohort described above were analyzed according to the established protocol. Additionally, urine samples from patients were analyzed for immune cells at different time points. The previously described effects of EPO on the immune system were also observed in this patient group. A previously reported increase in immune tolerance promoting cells could not be detected, possibly due to the immunosuppressive medication. We were able to demonstrate that EPO has different effects on various immune cells and alters metabolism. These changes lead to a reduced inflammatory response when these cells are stimulated (e.g., by infection or foreign tissue, as is the case in organ transplantation). In the urine, there was a decrease in cells that are typically associated with organ rejection. In conclusion, these results show that the immunosuppressive effects of EPO on immune cells can also be detected in kidney transplant patients and could potentially be used for individualized immunosuppressive strategies.
Publications
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Deep Phenotyping of Urinary Cells with Cytometry by Time of Flight Reveals CD8+CD38+ T Cells as a Biomarker to Detect T Cell-Mediated Rejection. Journal of the American Society of Nephrology, 35(10S).
Görlich, Nina; Metzke, Diana; Grothgar, Emil; Wagner, Leonie Felicitas; Choi, Mira; Ostendorf, Lennard; Mirkheshti, Pouneh; Klocke, Jan; Halleck, Fabian; Budde, Klemens; Cravedi, Paolo; Fribourg, Miguel; Amann, Kerstin U.; Baumgart, Sabine & Enghard, Philipp
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Kidney function after liver transplantation: the contrasting roles of inflammation and tubular repair. Frontiers in Transplantation, 3.
Görlich, Nina; Kim-Schulze, Seunghee; Kotanko, Peter; Grobe, Nadja; Wang, Xiaoling; Samans, Bjoern; Douglas, Joe; Enghard, Philipp; Molinari, Paolo; Fribourg, Miguel; Cravedi, Paolo & Levitsky, Josh
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The role of complement in kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International, 106(3), 369-391.
Vivarelli, Marina; Barratt, Jonathan; Beck, Laurence H.; Fakhouri, Fadi; Gale, Daniel P.; Goicoechea, de Jorge Elena; Mosca, Marta; Noris, Marina; Pickering, Matthew C.; Susztak, Katalin; Thurman, Joshua M.; Cheung, Michael; King, Jennifer M.; Jadoul, Michel; Winkelmayer, Wolfgang C.; Smith, Richard J.H.; Alberici, Federico; Antonucci, Luca; Avcin, Tadej ... & Zuccato, Marco
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“Deep phenotyping of urinary cells with cytometry by time of flight reveals CD8+CD38+ T cells as biomarker to detect T cell-mediated rejection” Poster and oral presentation Top Trainee Abstract Session ASN Kidney Week 10/2024 (American Society of Nephrology)
Görlich, Nina
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“Deep phenotyping of urinary cells with cytometry by time of flight reveals CD8+CD38+ T cells as biomarker to detect T cell-mediated rejection” Poster DGfN Kongress 09/2024 (Deutsche Gesellschaft for Nephrologie)
Görlich, Nina
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“LIPSTIC” Traces to Track Immune Cell Interaction. Transplantation, 108(12), 2289-2290.
Görlich, Nina & Cravedi, Paolo
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“Urin-Biomarker nach Transplantation” Oral presentation Basic Science Session DTG Kongress 11/2024 (Deutsche Transplantationsgesellschaft)
Görlich, Nina
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Patients With Immunoglobulin A Nephropathy Show Abnormal Frequencies of B Cell Subsets, Unconventional T Cells, and High Levels of Galactose-Deficient IgA1–Coated Gut Bacteria. Kidney International Reports, 10(2), 475-488.
Gentile, Micaela; Görlich, Nina; Lo, I.-Ju; Olson, N. Eric; McConnell, Mark; Pospiech, Johannes; Bohnenpoll, Tobias; Skroblin, Philipp; Radresa, Olivier; Andag, Uwe; Campbell, Kirk N.; Meliambro, Kristin; Sanchez-Russo, Luis; Verlato, Alberto; Fiaccadori, Enrico; Kim-Schulze, Seunghee; Lanau, Maria; Fernandez-Lorente, M. Loreto; Fribourg, Miguel ... & Cravedi, Paolo
