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临床试验/NCT06956469
NCT06956469尚未招募不适用

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

University Hospital, Bordeaux0 个研究点目标入组 75 人开始时间: 2025年6月15日最近更新:
适应症
干预措施

试验速览

阶段
不适用
状态
尚未招募
发起方
入组人数
75
主要终点
Memory B cell heterogeneity

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
主要目的
Prevention
盲法
None

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者
否

入选标准

  • •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

排除标准

  • •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)

研究组 & 干预措施

Sensitizing events : Pregnancy

Active Comparator

Patients who have been pregnant

干预措施: Identification of types of anti-HLA-specific memory LBs (Other)

Sensitizing events : Previous transplantation with thrombosis

Active Comparator

Previous transplantation with early transplantectomy due to thrombosis

干预措施: Identification of types of anti-HLA-specific memory LBs (Other)

Sensitizing events : Previous transplantation with antobody

Active Comparator

Previous transplantation with antibody-mediated rejection

干预措施: Identification of types of anti-HLA-specific memory LBs (Other)

Whitout any sensitizing event

Active Comparator

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

干预措施: Identification of types of anti-HLA-specific memory LBs (Other)

Sensitizing events : Transfusion

Active Comparator

Patients who received a blood transfusion

干预措施: Identification of types of anti-HLA-specific memory LBs (Other)

结局指标

主要结局

Memory B cell heterogeneity

时间窗: At inclusion

Memory B cell heterogeneity by single cell RNA sequencing

次要结局

  • Cytometry(At inclusion (Day 0), second visit (up to18 months) , third visit (up to 24 months))

研究者

发起方
University Hospital, Bordeaux
申办方类型
Other
责任方
Sponsor

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