Clinical trial NCT03994497: Evaluation of the Level of Expression of CD45RC on T Lymphocytes as a Predictive Biomarker of Acute Rejection After Renal Transplantation
Official title: Evaluation of the Level of Expression of CD45RC on T Lymphocytes as a Predictive Biomarker of Acute Rejection After Renal Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: End-stage Renal Disease
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2019-06-21
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: Chronic renal failure is a major public health problem in industrialized countries, due to its frequency - about 3 million patients in France - and its socio-economic impact. At the end stage of renal failure, renal transplantation is the best treatment, allowing an improvement in patient survival compared to treatment by extra-renal purification. Despite improved immunosuppressive strategies, allograft rejection is common in transplantation - between 15% and 25% in the first year - and is associated with lower renal graft survival.

Different risk factors for rejection have been well identified, such as the young age of the recipient or a high number of human leukocyte antigen (HLA) incompatibilities between the donor and the recipient. However, these risk factors do not accurately identify the risk of acute rejection in order to optimize and individualize immunosuppressive strategies.

Also, the search for biomarkers to predict allograft tolerance prior to transplant is a major goal in renal transplantation.

The onset of acute rejection is caused by the ability of the recipient's T cells to recognize alloantigens. The CD45 molecule is a highly expressed tyrosine phosphatase on the surface of the lymphocytes that plays an important role in the activation of the T cell.

Investigators showed that the level of expression of CD45RC on T lymphocytes was associated with the risk of acute rejection. Thus, from a retrospective cohort of 89 renal transplant patients followed, recipients with a high percentage of circulating CD8 lymphocytes expressing high CD45RC (CD45RChigh) before transplant had a 5 to 8-fold higher risk of developing acute rejection of allograft during follow-up (11-year average follow-up) compared to recipients with a low percentage of CD8+CD45RChigh.

The purpose of this study is to confirm the first retrospective results on a larger prospective and contemporary regional cohort.


Eligibility criteria: Inclusion Criteria:

* Patients over 18 and under 70 years old
* Patients in care for a first priority renal transplant.
* Patients with low immunological risk
* Patients with prior written informed consent

Exclusion Criteria:

* Poor understanding of the French language
* Pregnant, breastfeeding or partying women
* Persons deprived of liberty by an administrative or judicial decision
* Persons undergoing psychiatric care under duress
* Adults who are subject to a legal or non-state protection measure to express their consent

Primary outcomes:
measure: Number of patient with acute rejection diagnosis confirmed by anatomopathological analysis of a graft biopsy
timeFrame: 12 months
Secondary outcomes:
measure: Rate of CD45RC for patient with acute rejection suspicion
timeFrame: 12 months
measure: Rate of CD45RC on circulating T lymphocytes
timeFrame: from date of randomization until the date of acute rejection, up to 12 months
measure: Rate of CD45RC on circulating T lymphocytes the day of acute rejection
timeFrame: 12 months
measure: Rate of CD4, CD8, CD45RA, CD25, CD127, CD19 markers on T cells the day of acute rejection
timeFrame: 12 months
measure: anti-HLA antibodies' dosage at the time of acute rejection
timeFrame: 12 months
measure: cytokines' dosage
timeFrame: Day 1
Other outcomes:
Locations:
city: Angers
country: France
facility: Dr Anne-Sophie GARNIER
Study officials:
References: