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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.
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) :
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DSA positive patients without cAMR | Presence of DSA w/o cAMR |
| |
| DSA positive patients with cAMR | Presence of DSA w/ cAMR |
| |
| Stable patients | No DSA No cAMR |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Presence of DSA w/ cAMR | Other |
| ||
| Presence of DSA w/o cAMR |
| 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 |
| 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. |
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Inclusion criteria :
Non stable patients :
Stable patients :
Exclusion criteria :
- Patients that has not signed the consent form.
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100 kidney graft recipients with DSA or cAMR (renal dysfunction, positive DSA, allograft nephropathy), and 25 stable patients of 13 French transplantation centres.
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| Name | Affiliation | Role |
|---|---|---|
| Yannick LE MEUR, MD PhD | University Hospital, Brest | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Amiens | Amiens | 80054 | France | |||
| Chu Angers |
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| ID | Term |
|---|---|
| C419903 | 2-methyl-3-hydroxybutyryl-coenzyme A dehydrogenase |
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Whole Blood
| Other |
|
| No DSA No cAMR | Other |
|
| One year post inclusion |
| Angers |
| 49933 |
| France |
| CHU Brest | Brest | 29200 | France |
| CHU CAEN | Caen | 14033 | France |
| Chu Clermont Ferrand | Clermont-Ferrand | 63003 | France |
| CHU Limoges | Limoges | 87042 | France |
| APHP Hôpital Necker | Paris | 75743 | France |
| CHU Poitiers | Poitiers | 86021 | France |
| CHU Reims | Reims | 51092 | France |
| CHU Rennes | Rennes | 35033 | France |
| CHU Rouen | Rouen | 76230 | France |
| Hôpitaux Universitaires de Strasbourg | Strasbourg | 67091 | France |
| CHU Tours | Tours | 37044 | France |