B Cell Lymphocyte in Humoral Rejection and Alloimmunisation

Study Overview
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Brief Summary
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This study aims to better characterise B cell phenotype and functional abnormalities in kidney transplant patients producing donor specific antibody (DSA) and in those with chronic antibody mediated rejection (cAMR) and to search for a predictive tool (biomarker). The functional analysis will help to better understand B cell-dependant mechanisms implied in T cell proliferation and better target future treatments.

Detailed Description
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The principal objective is to better understand the B cell dependant mechanisms of the chronic antibody mediated rejection (cAMR). A particular focus will be done on the mechanisms that could explain the natural history of chronic humoral mediated rejection and of pathways from DSA negative status toward DSA positive status and from DSA positive status to histological lesions. The following will be undergone for three categories of patients (stable patients, DSA positive patients without cAMR and DSA positive patients with cAMR) : A phenotypic analysis of B cells of patients suffering from chronic humoral rejection or who are simply DSA positive. A functional analysis in autologous cultures in order to confirm our preliminary results. A functional analysis in a heterologous proliferation test aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR. A cytokine analysis (IL10, alpha-tumor necrosis factor, gamma-interferon dosing), for a better understanding of the mechanisms that are involved in the regulation of the T cell response that is induced by the B cells.

Conditions
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Renal Transplant

Intervention / Treatment
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* Other: Presence of DSA w/ cAMR
* Other: Presence of DSA w/o cAMR
* Other: No DSA No cAMR


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Non stable patients : Patient older than 18 years old. Patient which is the recipient of a renal transplant Patient who develops anti donor antibodies after the transplantation and / or suffering from a histologically-proven antibody mediated rejection. Patient who has signed an informed consent form Stable patients : Patient older than 18 years old. Patient that is the recipient of a renal transplant for more than one year Patient who has accepted to participate in the Brest Kidney graft recipient collection Patient that is not suffering from any rejection, that has a good renal function and a low proteinuria Patient that has not developed any DSA. Exclusion criteria : - Patients that has not signed the consent form.

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 positive patients without cAMR<br>Presence of DSA w/o cAMR | Other: Presence of DSA w/o cAMR<br> <br> |
| DSA positive patients with cAMR<br>Presence of DSA w/ cAMR | Other: Presence of DSA w/ cAMR<br> <br> |
| Stable patients<br>No DSA No cAMR | Other: No DSA No cAMR<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the ratio (percentage and absolute values) of mature LB subpopulations (LBm1 to LBm5) and of memory LB by specific labellings |  | At the inclusion day | 
| Evaluation of the proliferation of freshly isolated cells T in presence of autologous B cells |  | At the inclusion day | 
| Evaluation of the proliferation of T cells in a heterologous test | aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR | At the inclusion day | 
| cytokine analysis(IL10, alpha-Tumor Necrosis FActor, gamma-Interferon dosing) | for a better understanding of the mechanisms that are involved in the regulation of the T cell response that is induced by the B cells. | At the inclusion day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between phenotypic and functional evaluations, and clinical outcome |  | One year post inclusion | 
| comparison of the B cell subpopulations before and after rituximab treatment | In a subgroup of patients, the ones that will happen to be treated by rituximab for a rejection episode. | One year post inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplant, Immunology