We previously established a six-gene-based blood score associated with operational tolerance in kidney transplantation which was decreased in patients developing anti-HLA donor-specific antibodies (DSA). Herein, we aimed to confirm that this score is associated with immunological events and risk of rejection. We measured this using quantitative PCR (qPCR) and NanoString methods from an independent multicenter cohort of 588 kidney transplant recipients with paired blood samples and biopsies at one year after transplantation validating its association with pre-existing and de novo DSA.
View Article and Find Full Text PDFKiT-GENIE is a monocentric DNA biobank set up to consolidate the very rich and homogeneous DIVAT French cohort of kidney donors and recipients (D/R) in order to explore the molecular factors involved in kidney transplantation outcomes. We collected DNA samples for kidney transplantations performed in Nantes, and we leveraged GWAS genotyping data for securing high-quality genetic data with deep SNP and HLA annotations through imputations and for inferring D/R genetic ancestry. Overall, the biobank included 4217 individuals (n = 1945 D + 2,272 R, including 1969 D/R pairs), 7.
View Article and Find Full Text PDFThe human cytomegalovirus (HCMV) triggers both innate and adaptive immune responses, including protective CD8 αβT cells (CD8T) that contributes to the control of the infection. In addition to CD8T restricted by classical HLA class Ia molecules, HCMV also triggers CD8T recognizing peptides from the HCMV UL40 leader peptide and restricted by HLA-E molecules (HLA-E CD8T). This study investigated the frequency, phenotype and functions of HLA-E CD8T in comparison to the immunodominant HLA-A2 CD8T upon acute (primary or secondary infection) or chronic infection in kidney transplant recipients (KTR) and in seropositive (HCMV) healthy volunteer (HV) hosts.
View Article and Find Full Text PDFKidney transplant survival is shortened by chronic rejection and side effects of standard immunosuppressive drugs. Cell-based immunotherapy with tolerogenic dendritic cells has long been recognized as a promising approach to reduce general immunosuppression. Published trials report the safety and the absence of therapy-related adverse reactions in patients treated with tolerogenic dendritic cells suffering from several inflammatory diseases.
View Article and Find Full Text PDFBackground: The mechanisms regulating CD8 T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8 T cells that re-express CD45RA (TEMRA CD8 T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection.
Methods: We used single-cell proteomic profiling and functional testing of CD8 T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection.
Results: We showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8 T cells in blood and kidney graft biopsies.