Alloreactive Memory B Lymphocytes and Anti-HLA Sensitization
ConditionKidney Transplant
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity Hospital, Rouen
About this trial
In transplantation, B lymphocytes are major cellular players in the alloreactive humoral response through the production of antibodies targeting allogeneic HLA molecules expressed by the transplant. In subjects sensitized to HLA antigens, the contribution of pre-existing alloreactive memory B lymphocytes (Bmem) to allograft rejection phenomena after transplantation is now recognized. It has been proposed that the identification of these Bmem during the pre-transplant period could contribute to a better assessment of post-transplant immunological risk, allowing optimization of strategies to prevent humoral rejection. However, knowledge regarding the phenotypic and functional heterogeneity of Bmem as well as their clonal diversity is still extremely limited, not allowing discrimination between pathogenic and non-pathogenic alloreactive humoral responses. Such discrimination requires a better understanding of the modalities of differentiation of alloreactive B lymphocyte responses. To this end, this study aims to characterize the clonal, phenotypic and functional properties of alloreactive Bmem in subjects awaiting renal transplantation and sensitized to HLA antigens.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years
Rouen University Hospital patient monitored in the Nephrology and Kidney Transplantation Department, registered on the national kidney transplant waiting list
Carrier of HLA antibodies, including at least anti-HLA2, identified during the last screening
Notion of classic immune-promoting events including at least one previous transplant or pregnancy, or absence of a known immune-promoting event (naïve patient group)
Disqualifiers
Patients who have received rituximab in the previous year (B-cell depleting therapy)
Patients undergoing an HLA desensitization protocol using plasmapheresis and/or rituximab
Patients with an active infection
Persons deprived of their liberty by an administrative or judicial decision or persons placed under judicial protection/guardianship or curatorship
Trial population
Patients awaiting kidney transplantation and carrying HLA antibodies following immunizing events
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
Patients meeting HLA immunization criteria
Diagnostic testAt enrollment visit, a single sample of a volume of 50 ml of blood will be taken as part of routine care in order to directly and simultaneously explore the clonality (BCR repertoire), the phenotype of membrane markers and the transcriptome of Bmem alloreactive with respect to a restricted panel of HLA alleles chosen according to the HLA antibody reactivity profile of the patients analyzed
Treatment groups
No treatment groups listed
Trial outcomes
Primary outcomes
1
Level of heterogeneity of alloreactive Bmem targeting HLA alloantigens
The main objective is to determine the level of heterogeneity of alloreactive Bmem targeting HLA alloantigens of given specificities (primarily HLA-A2) in patients awaiting kidney transplantation and carrying HLA antibodies following immunizing events by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
Time frame
At enrollment visitSecondary outcomes
1
Evaluation of the level of phenotypic heterogeneity of alloreactive Bmem
To compare the level of phenotypic heterogeneity of alloreactive Bmem of given specificities (including HLA-A2) according to the immunization profile (hyperimmunization versus more restricted immunization) by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
Time frame
At enrollment visit2
Evaluation of the level of transcriptional heterogeneity of alloreactive Bmem
To compare the level of transcriptional heterogeneity of alloreactive Bmem of given specificities (including HLA-A2) according to the immunization profile (hyperimmunization versus more restricted immunization) by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
Time frame
At enrollment visit3
Clonality of Bmem specific to each HLA antigen tested
Evaluation of VDJ junction sequences of IgH genes coding for the BCR of alloreactive Bmem, analyzed with the IgBlast tool
Time frame
At enrollment visit4
Somatic mutations of the BCR of Bmem IgG+ or IgM+
Determine the number of somatic mutations of the BCR of Bmem IgG+ or IgM+ in each patient, and according to the IgBlast immunization profile (calculation of the average number of somatic mutations of the VDJ junction of the IgH genes)
Time frame
At enrollment visitSponsors and contacts
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Source ClinicalTrials.gov