ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation (ALL-T-COPIES)

Alloreactive t Cell Repertoire in Kidney Transplantation Recipients

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.

Study Overview

• Status: Recruiting
• Conditions: Transplant; Complication, Rejection; Renal Transplant Rejection; Immune Repertoire; Alloreactivity
• Intervention / Treatment: Diagnostic test: Mixed lymphocyte reaction

Detailed Description

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.

The diversity of the overall repertoire and alloreactive repertoire will be compared between these two groups.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Constantin N Aschauer, MD; Phone Number: 00434040043890; Email: constantin.aschauer@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Constantin N Aschauer, MD; Phone Number: 00434040043890; Email: constantin.aschauer@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Chronic kidney disease

Description

Inclusion Criteria:

• Kidney transplantation in our center

Exclusion Criteria:

• Donor not evaluated by our center

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Good transplant function; Kidney transplant recipients without histological signs of rejection.	Diagnostic test: Mixed lymphocyte reaction; Assessment of alloreactive T cell repertoire
Transplant Rejection; Kidney transplant recipinets experiencing a T cell mediated rejection episode.	Diagnostic test: Mixed lymphocyte reaction; Assessment of alloreactive T cell repertoire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rejection	biopsy proven rejection	12 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Rainer Oberbauer, MD, PhD, Medical University of Vienna

Publications and helpful links

General Publications

• Aschauer C, Jelencsics K, Hu K, Heinzel A, Gregorich MG, Vetter J, Schaller S, Winkler SM, Weinberger J, Pimenov L, Gualdoni GA, Eder M, Kainz A, Troescher AR, Regele H, Reindl-Schwaighofer R, Wekerle T, Huppa JB, Sykes M, Oberbauer R. Prospective Tracking of Donor-Reactive T-Cell Clones in the Circulation and Rejecting Human Kidney Allografts. Front Immunol. 2021 Oct 14;12:750005. doi: 10.3389/fimmu.2021.750005. eCollection 2021.
• Aschauer C, Jelencsics K, Hu K, Heinzel A, Vetter J, Fraunhofer T, Schaller S, Winkler S, Pimenov L, Gualdoni GA, Eder M, Kainz A, Regele H, Reindl-Schwaighofer R, Oberbauer R. Next generation sequencing based assessment of the alloreactive T cell receptor repertoire in kidney transplant patients during rejection: a prospective cohort study. BMC Nephrol. 2019 Sep 2;20(1):346. doi: 10.1186/s12882-019-1541-5.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ALL-T-COPIES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No