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临床试验/NCT03422224
NCT03422224招募中不适用

Alloreactive t Cell Repertoire in Kidney Transplantation Recipients

Medical University of Vienna1 个研究点 分布在 1 个国家目标入组 50 人开始时间: 2017年7月1日最近更新:
适应症

试验速览

阶段
不适用
状态
招募中
入组人数
50
试验地点
1
主要终点
Rejection

研究概览

简要总结

In this study, the investigators will establish a workflow to generate unique patterns of the donor-reactive T cell repertoire using mixed lymphocyte reactions to select alloreactive T cell clones prior to transplantation Tissue infiltrating as well as blood bound T cells will be characterized based on:

  1. Identification of donor-specific T cell receptor sequences pre- and post-transplant by in vitro expansion to determine unique patterns
  2. Quantification and comparison of donor-specific T cell clones in kidney biopsy and blood samples.
  3. Analysis of the TCR repertoire diversities derived from kidney biopsy and blood samples and association of repertoire diversities with the histomorphological phenotype of T cell mediated rejection.
  4. Identification of T cell subtypes within the donor-reactive population. The investigators specifically hypothesize that highly expanded donor-reactive T cell clones in both kidney tissue and blood samples at time of indication biopsy are associated with the histological phenotype of acute T cell mediated rejection. The investigators have previously shown that there is a strong correlation between highly expanded tissue-resident T cell clones and the repertoire found in periphery blood samples. To trace and quantify donor reactive T cells the investigators will apply a truly quantitative approach for immune repertoire profiling based on high- throughput sequencing. The investigators ultimate goal is to develop a diagnostic tool to assess alloreactive cellular immunoresponses based on peripheral blood samples.

详细描述

Kidney transplant recipients receiving a non lymphodepletional induction therapy at the investigators center will be included in this study.

Alloreactive T cells are defined prior to transplantation via a mixed lymphocyte reaction of donor and recipient PBMC's.

Following transplantation PBMC's will be sampled at management (3 and 12 months) and for-cause biopsies and fifteen patients with histological proven acute T cell mediated rejection will be compared to 15 patients without histopathological signs of alloimmune response in time matched for-cause biopsies.

T cell receptor beta chains of T cells found in the circulation and the allograft biopsy will be sequenced via Next generation sequencing.

Abundance of alloreactive T cells of the overall repertoire pre-and post-transplant and their presence in the allograft will be assessed.

研究设计

研究类型
Observational
观察模型
Case Control
时间视角
Prospective

入排标准

性别
All
接受健康志愿者

入选标准

  • Kidney transplantation in our center

排除标准

  • Donor not evaluated by our center

结局指标

主要结局

Rejection

时间窗: 12 months

biopsy proven rejection

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Rainer Oberbauer

Prof. Dr

Medical University of Vienna

研究点 (1)

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