Patients meeting HLA immunization criteria: At 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
Study summary
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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 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)
* Incompatible graft rate (IGR)
* IGR ≥ 85% (hyperimmunized patient group with anti-HLA polyreactivity) or
* IGR between 50% and 85% (immunized patient group with a more restricted repertoire of HLA reactivities) or
* IGR \< 50% (naïve patient group with no known history of immune-promoting events)
* Person who has read and understood the information letter and does not object Not participating in the study
* Affiliation to a social security scheme
Exclusion Criteria:
* 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
Primary outcome measure(s)
Level of heterogeneity of alloreactive Bmem targeting HLA alloantigens — At enrollment visit 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
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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