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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sensitizing events : Pregnancy | Active Comparator | Patients who have been pregnant |
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| Sensitizing events : Previous transplantation with thrombosis | Active Comparator | Previous transplantation with early transplantectomy due to thrombosis |
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| Sensitizing events : Previous transplantation with antobody | Active Comparator | Previous transplantation with antibody-mediated rejection |
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| Whitout any sensitizing event | Active Comparator | Patients who have anti-HLA antibodies without any sensitizing event identified |
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| Sensitizing events : Transfusion | Active Comparator | Patients who received a blood transfusion |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Identification of types of anti-HLA-specific memory LBs | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Memory B cell heterogeneity | Memory B cell heterogeneity by single cell RNA sequencing | At inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| Cytometry | Memory B cell heterogeneity by flow cytometry | At inclusion (Day 0), second visit (up to18 months) , third visit (up to 24 months) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Claire LEIBLER, MD | Contact | 05 57 82 21 46 | +33 | claire.leibler@chu-bordeaux.fr |
| Jonathan VISENTIN, PharmD, PhD | Contact | 05 57 82 24 | +33 | jonathan.visentin@chu-bordeaux.fr |
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