BMEM HLA: ORIGINS OF THE HETEROGENEITY OF ANTI-HLA MEMORY B CELLS IN KIDNEY TRANSPLANTATION (BmemHLA)

University Hospital of Bordeaux

Status: Begins enrollment this month

Conditions: Immunology; Kidney Transplantation

Treatments: Other: Identification of types of anti-HLA-specific memory LBs

Study type: Interventional

Funder types: Other

Identifiers

NCT06956469

CHUBX 2023/39

Details and patient eligibility

About

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. Our hypothesis is that these five contexts induce different types of memory B cells with different modalities of reactivation and post-transplant pathogenicity.

Full 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. We 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, we 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. We will first use an unbiased approach to test if anti-HLA memory B cells are heterogeneous. We 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. We 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.

Enrollment: 75 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 5 patient groups

Sensitizing events : Pregnancy

Active Comparator group

Description:

Patients who have been pregnant

Treatment:

Other: Identification of types of anti-HLA-specific memory LBs

Sensitizing events : Previous transplantation with thrombosis

Active Comparator group

Description:

Previous transplantation with early transplantectomy due to thrombosis

Treatment:

Other: Identification of types of anti-HLA-specific memory LBs

Sensitizing events : Previous transplantation with antobody

Active Comparator group

Description:

Previous transplantation with antibody-mediated rejection

Treatment:

Other: Identification of types of anti-HLA-specific memory LBs

Whitout any sensitizing event

Active Comparator group

Description:

Patients who have anti-HLA antibodies without any sensitizing event identified

Treatment:

Other: Identification of types of anti-HLA-specific memory LBs

Sensitizing events : Transfusion

Active Comparator group

Description:

Patients who received a blood transfusion

Treatment:

Other: Identification of types of anti-HLA-specific memory LBs