Clinical trial NCT03016455: B Cell Lymphocyte in Humoral Rejection and Alloimmunisation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Renal Transplant
Keywords: Kidney Transplant
Immunology
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
First posted: 2017-01-10
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 100 kidney graft recipients with DSA or cAMR (renal dysfunction, positive DSA, allograft nephropathy), and 25 stable patients of 13 French transplantation centres.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of the ratio (percentage and absolute values) of mature LB subpopulations (LBm1 to LBm5) and of memory LB by specific labellings
timeFrame: At the inclusion day
measure: Evaluation of the proliferation of freshly isolated cells T in presence of autologous B cells
timeFrame: At the inclusion day
measure: Evaluation of the proliferation of T cells in a heterologous test
timeFrame: At the inclusion day
measure: cytokine analysis(IL10, alpha-Tumor Necrosis FActor, gamma-Interferon dosing)
timeFrame: At the inclusion day
Secondary outcomes:
measure: Correlation between phenotypic and functional evaluations, and clinical outcome
timeFrame: One year post inclusion
measure: comparison of the B cell subpopulations before and after rituximab treatment
timeFrame: One year post inclusion
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Angers
country: France
facility: Chu Angers
city: Brest
country: France
facility: CHU Brest
city: Caen
country: France
facility: CHU CAEN
city: Clermont Ferrand
country: France
facility: Chu Clermont Ferrand
city: Limoges
country: France
facility: CHU Limoges
city: Paris
country: France
facility: APHP Hôpital Necker
city: Poitiers
country: France
facility: CHU Poitiers
city: Reims
country: France
facility: CHU Reims
city: Rennes
country: France
facility: CHU Rennes
city: Rouen
country: France
facility: CHU Rouen
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: University Hospital, Brest
name: Yannick LE MEUR, MD PhD
role: STUDY_DIRECTOR
References: