H2020Индивидуална стипендия2019–2021

KiT-FIG · Kidney Transplantation - Functional ImmunoGenomics

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-07-01 → 2021-06-30
Финансиране от ЕС: 196 708 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Генетичните особености на HLA молекулите и техните рецептори определят как имунната система реагира на трансплантиран бъбрек. Разбирането на тези процеси помага за по-доброто управление на пациентите и по-точното подбиране на подходящи донори.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Kidney Transplantation - Functional ImmunoGenomics

Chronic renal failure affects ~10% of the world population and can progressively lead to end-stage renal disease (ESRD) requiring replacement therapy (dialysis or transplantation). Kidney transplantation is the best treatment for ESRD. The one-year survival of kidney transplant is now 90% and the graft half-life is about 10 years. However, despite these enormous progresses of immunosuppressive treatments, the host immune response against the graft still leads to rejection in many cases. This public health issue is critical considering that organs are a rare resource. Overall, the triggers leading to rejection are still largely unknown and need to be further studied. The HLA (human leukocyte antigen) molecule is the immunodominant antigen for both humoral and cellular alloreactivity. The number of HLA allelic differences between donor and recipient (mismatches) is strongly linked to graft survival, hence HLA compatibility between donor and recipient is essential. Nevertheless, mismatches do not explain all rejections and the intrinsic effect of HLA alleles, beyond these mismatches, remains elusive. Altogether, I hypothesize that HLA plays a major role in post-renal transplant complications and graft dysfunction, beyond HLA mismatches. Exploring the HLA diversity and complexity (alleles, haplotypes), but also aspects of regulation/expression and KIR receptors is definitely a present-day research project and will allow us to better understand cellular and humoral rejections and provide new insights in transplanted patients management and graft allocation for example by selecting potential less immunogenic HLA alleles. The Kidney Transplantation - Functional ImmunoGenomics (KiT-FIG) project was designed to answer 2 main challenges: 1) to develop innovative methods of HLA statistical inference to gain precision and generate additional immunogenomic; 2) to apply these novel biostatistical and bioinformatic methods to the different immunological outcomes related to renal transplantation (chronic rejection, tolerance) to improve graft survival and patient management.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

NANTES UNIVERSITE · NantesКоординаторФранция