B Cell Lymphocyte in Humoral Rejection and Alloimmunisation

• Conditions: Renal Transplant

• 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.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2016-08-30
• Study First Submitted QC: 2017-01-09
• Study First Posted: 2017-01-10
• Status Verified: 2017-04
• Last Update Submitted: 2017-05-02
• Last Update Posted: 2017-05-04
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

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 Amiens; 🇫🇷 Amiens, France

Chu Angers; 🇫🇷 Angers, France

CHU Brest; 🇫🇷 Brest, France

CHU CAEN; 🇫🇷 Caen, France

Chu Clermont Ferrand; 🇫🇷 Clermont Ferrand, France

CHU Limoges; 🇫🇷 Limoges, France

APHP Hôpital Necker; 🇫🇷 Paris, France

CHU Poitiers; 🇫🇷 Poitiers, France

CHU Reims; 🇫🇷 Reims, France

CHU Rennes; 🇫🇷 Rennes, France

Scroll for more (3 remaining)