Kidney Transplantation - Functional ImmunoGenomics

ended

Chronic renal failure affects ~10% of the world population and can gradually lead to end-stage renal disease (ESRD) requiring kidney transplantation. Despite the huge progress of immunosuppressive treatments, the host immune response against the graft still leads to rejection in many cases, with an average graft half-life of 10 years. Triggers leading to graft rejection are still largely unknown and need to be studied beyond the well-recognized impact of HLA mismatches. I propose here to explore the effect of functional immunogenomic parameters beyond HLA mismatches (HLA alleles, HLA gene expression regulation, KIR...) on kidney transplantation outcomes (cellular and humoral rejections, tolerance). To achieve this present-day clinical challenge, I will combine innovative bioinformatics tools and modern genomics to perform cutting edge association studies: the Kidney Transplantation - Functional ImmunoGenomics (KiT-FIG) project. KiT-FIG ultimate goal is to provide new evidence to improve graft allocation and transplanted patients’ management. Objective A is to develop innovative methods of HLA statistical inference to gain precision and generate additional functional immunogenomic parameters. Objective B is to apply these novel methods to investigate the impact of immunogenetics on immunological outcomes related to kidney transplantation. This objective will rely on genetic association studies to unlock the major scientific challenge of large and unexplained variability observed in renal graft survival. KiT-FIG ambitions to develop new innovative bioinformatic and biostatistics tools to capture the complexity of HLA-related immune responses. These tools will be freely accessible to the community to expand immunogenetic studies of other diseases. The implementation of these tools in the context of kidney transplantation outcomes will increase the understanding of underlying immunological mechanisms and will contribute to improve graft survival and patient management.