B Cell Lymphocyte in Humoral Rejection and Alloimmunisation
- Conditions
- Renal Transplant
- Interventions
- Other: Presence of DSA w/o cAMROther: No DSA No cAMROther: Presence of DSA w/ cAMR
- Registration Number
- NCT03016455
- Lead Sponsor
- University Hospital, Brest
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 125
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description DSA positive patients without cAMR Presence of DSA w/o cAMR Presence of DSA w/o cAMR Stable patients No DSA No cAMR No DSA No cAMR DSA positive patients with cAMR Presence of DSA w/ cAMR Presence of DSA w/ cAMR
- Primary Outcome Measures
Name Time Method 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 cytokine analysis(IL10, alpha-Tumor Necrosis FActor, gamma-Interferon dosing) At the inclusion day 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.
Evaluation of the proliferation of T cells in a heterologous test At the inclusion day aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR
- Secondary Outcome Measures
Name Time Method comparison of the B cell subpopulations before and after rituximab treatment One year post inclusion In a subgroup of patients, the ones that will happen to be treated by rituximab for a rejection episode.
Correlation between phenotypic and functional evaluations, and clinical outcome One year post inclusion
Trial Locations
- Locations (13)
CHU CAEN
🇫🇷Caen, France
CHU Rouen
🇫🇷Rouen, France
Chu Angers
🇫🇷Angers, France
APHP Hôpital Necker
🇫🇷Paris, France
CHU Amiens
🇫🇷Amiens, France
Chu Clermont Ferrand
🇫🇷Clermont Ferrand, France
CHU Poitiers
🇫🇷Poitiers, France
CHU Reims
🇫🇷Reims, France
Hôpitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France
CHU Tours
🇫🇷Tours, France
CHU Brest
🇫🇷Brest, France
CHU Limoges
🇫🇷Limoges, France
CHU Rennes
🇫🇷Rennes, France