Alloreactive Memory B Lymphocytes and Anti-HLA Sensitization in Kidney Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 51
- 试验地点
- 2
- 主要终点
- Level of heterogeneity of alloreactive Bmem targeting HLA alloantigens
研究概览
简要总结
In transplantation, B lymphocytes are major cellular players in the alloreactive humoral response through the production of antibodies targeting allogeneic HLA molecules expressed by the transplant. In subjects sensitized to HLA antigens, the contribution of pre-existing alloreactive memory B lymphocytes (Bmem) to allograft rejection phenomena after transplantation is now recognized. It has been proposed that the identification of these Bmem during the pre-transplant period could contribute to a better assessment of post-transplant immunological risk, allowing optimization of strategies to prevent humoral rejection. However, knowledge regarding the phenotypic and functional heterogeneity of Bmem as well as their clonal diversity is still extremely limited, not allowing discrimination between pathogenic and non-pathogenic alloreactive humoral responses. Such discrimination requires a better understanding of the modalities of differentiation of alloreactive B lymphocyte responses. To this end, this study aims to characterize the clonal, phenotypic and functional properties of alloreactive Bmem in subjects awaiting renal transplantation and sensitized to HLA antigens.
详细描述
The hypothesis underlying this study is that analysis of the heterogeneity of alloreactive memory B cells (Bmem) in patients carrying HLA antibodies under different levels of HLA immunization intensity, corresponding to varying degrees of exposure to HLA alloantigens, may provide insights into the mechanisms governing the formation of the overall alloreactive B-cell repertoire.
Two categories of patients sensitized to HLA antigens following immunizing events (at least one transplantation or pregnancy) and awaiting kidney transplantation will be specifically investigated:
Hyperimmunized patients, defined by an incompatible graft rate (IGR) ≥ 85%, carrying a broad HLA antibody repertoire.
Immunized patients with an IGR between 50% and 85%, carrying a more restricted HLA antibody repertoire.
These two groups represent distinct levels of exposure to HLA alloantigens. Patients exposed exclusively to immunizing events other than transplantation or pregnancy will not be included because of the absence of detectable alloreactive Bmem in such settings.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
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
- •Age ≥ 18 years
- •Rouen University Hospital patient monitored in the Nephrology and Kidney Transplantation Department, registered on the national kidney transplant waiting list
- •Carrier of HLA antibodies, including at least anti-HLA2, identified during the last screening
- •Notion of classic immune-promoting events including at least one previous transplant or pregnancy, or absence of a known immune-promoting event (naïve patient group)
- •Incompatible graft rate (IGR)
- •IGR ≥ 85% (hyperimmunized patient group with anti-HLA polyreactivity) or
- •IGR between 50% and 85% (immunized patient group with a more restricted repertoire of HLA reactivities) or
- •IGR < 50% (naïve patient group with no known history of immune-promoting events)
- •Person who has read and understood the information letter and does not object Not participating in the study
- •Affiliation to a social security scheme
排除标准
- •Patients who have received rituximab in the previous year (B-cell depleting therapy)
- •Patients undergoing an HLA desensitization protocol using plasmapheresis and/or rituximab
- •Patients with an active infection
- •Persons deprived of their liberty by an administrative or judicial decision or persons placed under judicial protection/guardianship or curatorship
结局指标
主要结局
Level of heterogeneity of alloreactive Bmem targeting HLA alloantigens
时间窗: At enrollment visit
The main objective is to determine the level of heterogeneity of alloreactive Bmem targeting HLA alloantigens of given specificities (primarily HLA-A2) in patients awaiting kidney transplantation and carrying HLA antibodies following immunizing events by evaluating the number of alloreactive Bmem clusters identified (in all patients) on the basis of their gene expression profiles (bioinformatics analysis of expression data with the open source Seurat suite
次要结局
- Evaluation of the level of phenotypic heterogeneity of alloreactive Bmem(At enrollment visit)
- Ratio of the number of Bmem IgM+/IgG+(At enrollment visit)
- Evaluation of the level of transcriptional heterogeneity of alloreactive Bmem(At enrollment visit)
- Clonality of Bmem specific to each HLA antigen tested(At enrollment visit)
- Somatic mutations of the BCR of Bmem IgG+ or IgM+(At enrollment visit)