Immune Response in Desensitized Patients

NCT05785936 | Unknown DMC

• 1 other identifier: 2022-A02445-38
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Kidney Transplant Rejection

Keywords

HLA sensitization; Desensitization; Antibody secreting cells

Outcome Measures

Primary Outcomes (4)

• Change in Flow Cytometry analyses of Peripheral Blood Mononuclear Cells

  Change of the percentage of "antibody secreting cells" (plasmablasts) over time

  Before desensitization, at the time of transplantation and Before desensitization, at the time of transplantation and post transplantation

• Change in Anti HLA B-cell ELISpot response

  Change in the number of Spot over time

  Before desensitization, at the time of transplantation and Month 3, Month 6 and Month 12 post transplantation

• Change in Flow Cytometry analyses of medullary cells

  Change in the percentage of "antibody secreting cells" (plasmablasts) over time

  The first day of desensitization and at the day of kidney transplantation

• Change in analyses of RNA expression on renal histology

  CHange in percentage of gene expression using Nanostring technology

  Month1, Month 3 and Month 12 post transplantation

Study Arms (3)

Highly sensitized and desensitized kidney transplanted group

Patient that were HLA desensitized for kidney transplantation

Procedure: Desensitization

Highly sensitized and non-desensitized kidney transplanted group

Patient that were not HLA desensitized for kidney transplantation but were highly sensitized and received a kidney graft due to local priority system

Healthy donors

Interventions

Desensitization PROCEDURE

Patients that received apheresis and anti-cluster of differentiation antigen 20 for desensitization priori to kidney transplantation

Highly sensitized and desensitized kidney transplanted group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

15 highly sensitized patients: 10 that received desensitization before kidney transplan tation and 5 that were not desensitized before kidney transplantation. 5 healthy donors

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Patients who object to the use of their data and/or samples in the research
• All protected persons: pregnant women, parturients, nursing mothers, persons deprived of liberty by judicial or administrative decision, persons under legal protection.
• Subject under administrative or judicial supervision
• Subject unable to be contacted in case of emergency

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood for PBMC (peripheral mononuclear cells) Medullary samples Lymph node samples

MeSH Terms

Interventions

Desensitization, Psychologic

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: March 27, 2023
• Study Start: May 1, 2023
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: March 29, 2023

Record last verified: 2023-03