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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplantation; Immunology
• Intervention / Treatment: Other: Identification of types of anti-HLA-specific memory LBs

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.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claire LEIBLER, MD; Phone Number: +33 05 57 82 21 46; Email: claire.leibler@chu-bordeaux.fr
• Study Contact Backup: Name: Jonathan VISENTIN, PharmD, PhD; Phone Number: +33 05 57 82 24; Email: jonathan.visentin@chu-bordeaux.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sensitizing events : Pregnancy; Patients who have been pregnant	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.
Active Comparator: Sensitizing events : Previous transplantation with thrombosis; Previous transplantation with early transplantectomy due to thrombosis	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.
Active Comparator: Sensitizing events : Previous transplantation with antobody; Previous transplantation with antibody-mediated rejection	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.
Active Comparator: Whitout any sensitizing event; Patients who have anti-HLA antibodies without any sensitizing event identified	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.
Active Comparator: Sensitizing events : Transfusion; Patients who received a blood transfusion	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Memory B cell heterogeneity	Memory B cell heterogeneity by single cell RNA sequencing	At inclusion

Secondary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2025
• Primary Completion (Estimated): June 15, 2025
• Study Completion (Estimated): December 15, 2028

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: April 25, 2025
• First Posted (Actual): May 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Transplantation; Kidney; Anti-HLA antibodies; Memory B Cell; Allogeneic events
• Other Study ID Numbers: CHUBX 2023/39

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No