Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures

Immune tolerance is involved physiologically in pregnancy and disrupted in autoimmunity, organ rejection, and graft-versus-host disease (GvHD). In transplantation setting, operational tolerance has been inferred in patients who develop tolerance without a need for immunosuppressants. However, mechanisms underlying operational tolerance in Humans are poorly understood. Using two cohorts of patients who underwent an allo-HSCT from HLA-identical siblings, we used multi-omics approach to decipher immune landscape associated with tolerance in recipients and their related donors. We analyzed two cohorts of patients, one monocentric from Saint Louis hospital (cohort 1, n=41) and one multicenric from the national Cryostem consortium biological collection (cohort 2, n=69). We proceed to deep immunophenotyping of peripheral blood mononuclear cell using mass cytometry, RNA sequencing analysis and metabolomics profiling of plasma in both recipients and related donors. The aim of this study is to determine the evolution of immune landscape after allogeneic HSCT by comparison with healthy donors, and to identify specific biological mechanism associated with immune tolerance in patients. PBMC total RNAseq analysis of recipients and their relative donors from patients eligible for hematopoietic stem cell transplantation from an HLA-identical sibling donor. Two cohorts: one monocentric discovery cohort (41 complete couples) and one multicentric confirmation cohort (69 complete couples). Two time-point: 15 days before transplantation for donor and 1 to 2 years after transplantation for recipients. Among patients included in this study, RNA seq data were available in 32 paired donors and recipients from cohort 1, and 62 paired donors and recipients from cohort 2.