BmemHLA : Origins of the Heterogeneity of the Anti-HLA Memory B Cells in Kidney Transplantation

Overview

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.

Interventions

• Other Identification of types of anti-HLA-specific memory LBs
  Using blood sample, it will be 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. It will be 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.

Primary outcome measures

• Memory B cell heterogeneity [Time frame: At inclusion]

Secondary outcome measures (1)

• Cytometry [Time frame: At inclusion (Day 0), second visit (up to18 months) , third visit (up to 24 months)]

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06956469 · CHUBX 2023/39

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗