Alloreactive Memory B Lymphocytes and Anti-HLA Sensitization in Kidney Transplantation
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.
• 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