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NCT Number: NCT06956469

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

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.

Primary outcomes

  1. Memory B cell heterogeneity

    Time frame: At inclusion

    Memory B cell heterogeneity by single cell RNA sequencing

Secondary outcomes

  1. Cytometry

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

    Memory B cell heterogeneity by flow cytometry

Study contacts

Contact information is provided by the study sponsor or research team.

Claire LEIBLER, MD

CONTACT

[email protected]

05 57 82 21 46 ext. +33

Jonathan VISENTIN, PharmD, PhD

CONTACT

[email protected]

05 57 82 24 ext. +33

Sponsors and collaborators

Lead sponsor

University Hospital, Bordeaux

Other

Registry information

Acronym: BmemHLA

Important dates

Study start
2025
Primary completion
2025
Study completion
2028
First posted
May 4, 2025
Registry last updated
May 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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