Nanoparticle for DSA Removal

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Donor-specific Anti-human Leukocyte Antigen Antibodies (DSA) Re-moval From Patient Blood Using Functionalized Nanoparticles - an ex Vivo Feasibility and Proof of Principle Study

Conditions
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Kidney Failure, Presence of Donor Specific Antibodies

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSA in the blood as detected by Luminex® Adults (>18 years old) Informed written consent Exclusion Criteria: Inability to follow the procedures of the study, due to language problems, psychological disorders, social conditions or dementia Pregnancy and/or breast feeding Unwillingness to participate in this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DSA in patients with kidney failure<br>Patients on kidney transplantation waiting list with DSA detected by Luminex (and mean fluorescence intensity (MFI) > 1000) in their blood. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donor specific antibodies, Kidney transplantation, Coated nanoparticles