Clinical trial NCT06956469: BmemHLA : Origins of the Heterogeneity of the Anti-HLA Memory B Cells in Kidney Transplantation
Official title: BmemHLA : Origins of the Heterogeneity of the Anti-HLA Memory B Cells in Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Kidney Transplantation
Immunology
Keywords: Kidney
Memory B Cell
Anti-HLA antibodies
Allogeneic events
Transplantation
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2025-05-04
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will describe the transcriptomic and phenotypic characteristics of anti-HLA memory B cells by comparing five groups of patients awaiting renal transplantation: patients with a single history of pregnancy, transfusion or failure of a first renal transplant requiring transplantectomy within 3 months of transplantation, or after 3 months, and patients without an immunizing allogeneic event. The hypothesis is that these five contexts induce different types of memory B cells with different modalities of reactivation and post-transplant pathogenicity.

Detailed description: In kidney transplantation, the production of anti-HLA antibodies directed against the donor (DSA for Donor Specific Antibodies) can be responsible for humoral rejection, the main cause of long-term graft loss. Reactivation of anti-HLA memory B cells after transplantation is thought to play a major role in DSA production and the occurrence of humoral rejection. The investigators hypothesize that the nature and the function of anti-HLA memory B cells could differ depending on how they were initially generated. Several sensitizing events can lead to the production of anti-HLA memory B cells, but differ in terms of their inflammatory environment and the duration of allo-antigen exposure: pregnancy, transfusion or a previous transplantation. For the last group, the investigators want to distinguish two situations: kidney-transplanted patients that had an early transplantectomy due to thrombosis or that had an antibody-mediated rejection. Finally, patients can have anti-HLA antibodies without any sensitizing event identified. The investigators will first use an unbiased approach to test if anti-HLA memory B cells are heterogeneous. The investigators will perform single cell RNA sequencing of sorted anti-HLA B cells, identified with HLA tetramers, of five groups of patients based on their immunization histories. The investigators will further perform a phenotypic characterization of the tetramer+ anti-HLA B cells using spectral cytometry to study their nature and identify novel markers of memory subgroups.

Eligibility criteria: Inclusion Criteria:

* Adult kidney transplantation candidate at CHU de Bordeaux
* Sensitized against class I HLA
* Only on type of sensitizing event among : transfusion, pregnancy, previous transplantation, no senitizing event

Exclusion Criteria:

* Pediatric kidney transplantation candidate at CHU de Bordeaux
* Rituximab injection
* Ongoing treatment with immunosuppressive drugs
* Non-cutaneous carcinoma, chronic viral infection
* Acute infection
* Recent vaccination (\<1 month)

Primary outcomes:
measure: Memory B cell heterogeneity
timeFrame: At inclusion
Secondary outcomes:
measure: Cytometry
timeFrame: At inclusion (Day 0), second visit (up to18 months) , third visit (up to 24 months)
Other outcomes:
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