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Magnetic nanoparticles, coated with human leukocyte antigens (HLA) to capture anti-HLA antibodies with donor specificity (donor-specific antibodies, DSA), will be tested ex-vivo.
This project aims at developing a new method using human leukocyte antigens (HLA)-coated magnetic nanoparticles to remove donor-specific antibodies (DSA) from the patients' blood ex vivo, while trying to keep the blood unaffected after exposure to the particles.
Nanoparticles will be engineered and tested ex vivo. While nanoparticles were successfully coated with macromolecules such as antibodies in the past, this is a new approach, which will be performed by the research group.
The goal of this project is to capture DSA in patient blood ex vivo and to remove them by magnetic separation. Efficacy and safety of this procedure will be assessed, especially the interaction of these novel particles with other blood components such as coagulation factors or effector cells, which could produce inflammatory mediators. According analyses are initiated and carried out.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DSA in patients with kidney failure | Patients on kidney transplantation waiting list with DSA detected by Luminex (and mean fluorescence intensity (MFI) > 1000) in their blood. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of DSA removed in a blood sample using HLA-coated magnetic nanoparticles | Quantification of DSA removal using HLA-coated magnetic nanoparticles in comparison with blood treated with control nanoparticles (without HLA coating). | 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| Blood coagulation (rotational thromboelastometry ROTEM, plasma clotting time) before and after treatment with HLA-coated magnetic nanoparticles | Coagulation parameters as described will be evaluated in blood samples. The same analyses will be repeated after exposure to HLA-coated magnetic nanoparticles. | 1 day |
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Inclusion Criteria:
Exclusion Criteria:
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Patients suffering from kidney failure with DSA.
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| Name | Affiliation | Role |
|---|---|---|
| Beatrice Beck Schimmer, Prof | University of Zurich | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Zurich, Division of Anaesthesiology | Zurich | Canton of Zurich | 8091 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29315141 | Background | Wan SS, Ying TD, Wyburn K, Roberts DM, Wyld M, Chadban SJ. The Treatment of Antibody-Mediated Rejection in Kidney Transplantation: An Updated Systematic Review and Meta-Analysis. Transplantation. 2018 Apr;102(4):557-568. doi: 10.1097/TP.0000000000002049. | |
| 26979124 | Background | Herrmann IK, Beck-Schimmer B, Schumacher CM, Gschwind S, Kaech A, Ziegler U, Clavien PA, Gunther D, Stark WJ, Graf R, Schlegel AA. In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios. Nanomedicine (Lond). 2016 Apr;11(7):783-96. doi: 10.2217/nnm.16.22. Epub 2016 Mar 16. |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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Bloodsample
| Inflammatory blood mediators (IL-6, MCP-1) before and after treatment with HLA-coated magnetic nanoparticles |
Inflammatory parameters as described will be evaluated in blood samples. The same analyses will be repeated after exposure to HLA-coated magnetic nanoparticles. |
| 1 day |
| 26434758 | Background | Jacobson M, Roth Z'graggen B, Graber SM, Schumacher CM, Stark WJ, Dumrese C, Mateos JM, Aemisegger C, Ziegler U, Urner M, Herrmann IK, Beck-Schimmer B. Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial cells: influence of shear stress and endothelial activation. Nanomedicine (Lond). 2015;10(24):3537-46. doi: 10.2217/nnm.15.172. Epub 2015 Oct 5. |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |