Cell-based Assays for Antibody-mediated Transplant Rejection

Study Overview
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Brief Summary
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Goal: The goal of this study is to validate blood tests, which can detect antibody-mediated rejection (ABMR) after renal transplantation. These cell based assays measure CD154-expressing alloantigen-specific B-cells and their subsets in peripheral blood of adult renal transplant recipients. Thirty recipients will be enrolled at two transplant centers, 10 each with ABMR, T-cell mediated rejection (TCMR), and no rejection. Each subject will be sample twice, before and after rejection. Donor-specific anti-HLA antibodies will also be measured with single antigen beads.

Detailed Description
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This cross-sectional open label study will evaluate whether alloantigen-specific B-cells and their subsets which express CD154 are associated with antibody-mediated rejection after first time renal transplantation in adult recipients. Control groups include adult renal transplant recipients with T-cell-mediated rejection, and without rejection of any type. Alloantigen-specific B-cells will be measured after stimulation of recipient peripheral blood leukocytes with those from corresponding donor and HLA-non-identical reference cells. Thirty total subjects will be enrolled after IRB-approved informed consent, 15 at each of two sites. These subjects will include ten each with biopsy-proven ABMR and TCMR and ten with no rejection. Each subject will be sampled twice, before and after treatment rejection, at intervals no less than 30 days, and not to exceed 90 days. B-cells subsets will include those that also express cytokines, and those that are categorized as memory or naive, and their isotope switched or unswitched subsets, transitional B-cells or plasmablasts, etc.

Official Title
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Validating Cell-based Assays for ABMR After Renal Transplantation

Conditions
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Antibody-Mediated Graft Rejection

Intervention / Treatment
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* Diagnostic Test: Alloantigen-specific B-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IRB-approved informed consent. Adults (>18 yr to 70 years) Primary renal transplant recipients with biopsy-proven ABMR, TCMR or recipients with no rejection Exclusion Criteria: Lack of informed consent Concomitant BK virus infection Vulnerable populations including children <18 yr, pregnant women, and prisoners

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ABMR<br>Biopsy-proven ABMR-Banff criteria, with or without Complement binding donor-specific anti-HLA antibodies | Diagnostic Test: Alloantigen-specific B-cells<br>* Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry<br>|
| TCMR<br>Biopsy-proven TCMR-Banff 1A, 1B, 2 and 3 | Diagnostic Test: Alloantigen-specific B-cells<br>* Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry<br>|
| No Rejection<br>Biopsy-proven, or clinical criteria | Diagnostic Test: Alloantigen-specific B-cells<br>* Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody-mediated rejection | Biopsy-proven antibody-mediated rejection after primary renal transplantation | up to 90 days per subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-cell mediated rejection (TCMR) | Biopsy-proven TCMR after primary renal transplantation | up to 90 days per subject | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody mediated Rejection, Renal Transplantation, Adults, CD154, B-cells, B-cell subsets, alloantigen-specific