Immune Response in Desensitized Patients

Kidney transplantation is the best treatment for chronic renal failure in terms of morbidity and mortality, quality of life for patients and health economics. Sensitization with anti-Human Leukocyte Antigen antibodies is a barrier to access to transplantation.

Highly-sensitized patients wait 2 to 3 times longer on the waiting list with important health and economic consequences. Desensitization strategies by apheresis techniques allow access to a transplant with a negative crossmatch (absence of specific HLA antibodies against their donor) on the day of the transplant.

The main objective of this study is to assess the impact of desensitization on the antibody memory immune response in highly sensitized patients awaiting kidney transplantation.

The analyses will be based on samples from the 20 patients (10 desensitized transplanted patients, 5 highly sensitized non-desensitized transplanted patients and 5 healthy donors) at the University Hospital of Grenoble, France.

Analyses will include phenotypic and immuno-metabolic analysis by flow cytometry of antibody-secreting cells, a functional analysis by anti HLA ELISpot B technique and histological analysis of post-kidney transplantation follow-up renal biopsies with gene expression mapping (RNA tissue labeling using the Nanostring technique) within the renal parenchyma.


Eligibility Criteria:
Inclusion Criteria:

* Adult patients (age \>18 years) with end-stage renal disease (on hemodialysis or peritoneal dialysis or stage V chronic kidney disease) who are candidates for pre-renal transplantation desensitization from living or deceased donors.
* For women of childbearing age: a plasma pregnancy test before inclusion is mandatory. Highly effective contraception for women of childbearing age is required throughout the study period:
* combined hormonal contraception (containing estrogen and progestin)
* contraception associated with ovulation inhibition :

  * oral
  * intravaginal
  * transdermal
* Progestin-only hormonal contraception associated with ovulation inhibition:

  * oral
  * injectable
  * implantable
* intrauterine device (IUD) - intrauterine hormone delivery system (IUS)
* bilateral tubal occlusion
* vasectomized partner
* sexual abstinence
* Have signed the DELIGHT protocol consent.
* Affiliated to a social security system
* Can be contacted in case of emergency
* For the control groups :
* Healthy controls from blood samples (centrifugation ring) from the French Blood Agency. The use of healthy controls is necessary to compare immunological analyses to a reference group without immunosuppression.
* Highly sensitized kidney transplant patients without the need for de-immunization. Hyperimmunization is defined by a Panel Reactive Antibody score \> 85%. Transplantation can be from deceased or living donors.

Exclusion Criteria:

* Patients who object to the use of their data and/or samples in the research
* Patients having received an immunosuppressive treatment in the 12 months preceding the inclusion
* All protected persons: pregnant women, parturients, nursing mothers, persons deprived of liberty by judicial or administrative decision, persons under legal protection.
* Subjects in a period of exclusion from another study
* Subject under administrative or judicial supervision
* Subject unable to be contacted in case of emergency