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) : * 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.
Study Type
OBSERVATIONAL
Enrollment
125
CHU Amiens
Amiens, France
COMPLETEDChu Angers
Angers, France
COMPLETEDCHU Brest
Brest, France
Evaluation of the ratio (percentage and absolute values) of mature LB subpopulations (LBm1 to LBm5) and of memory LB by specific labellings
Time frame: At the inclusion day
Evaluation of the proliferation of freshly isolated cells T in presence of autologous B cells
Time frame: 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
Time frame: 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.
Time frame: At the inclusion day
Correlation between phenotypic and functional evaluations, and clinical outcome
Time frame: 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.
Time frame: One year post inclusion
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CHU CAEN
Caen, France
COMPLETEDChu Clermont Ferrand
Clermont-Ferrand, France
COMPLETEDCHU Limoges
Limoges, France
WITHDRAWNAPHP Hôpital Necker
Paris, France
COMPLETEDCHU Poitiers
Poitiers, France
COMPLETEDCHU Reims
Reims, France
COMPLETEDCHU Rennes
Rennes, France
COMPLETED...and 3 more locations