BmemHLA : Origins of the Heterogeneity of the Anti-HLA Memory B Cells in Kidney Transplantation
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
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
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
Previous transplantation with antibody-mediated rejection
干预措施: Identification of types of anti-HLA-specific memory LBs (Other)
Whitout any sensitizing event
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
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))
