ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation

NCT ID: NCT03422224

Last Updated: 2023-10-23

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2024-07-31

Brief Summary

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.

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.

Conditions

Renal Transplant Rejection; Immune Repertoire; Transplant; Complication, Rejection; Alloreactivity

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Good transplant function

Kidney transplant recipients without histological signs of rejection.

Mixed lymphocyte reaction

Intervention Type: DIAGNOSTIC_TEST

Assessment of alloreactive T cell repertoire

Transplant Rejection

Kidney transplant recipinets experiencing a T cell mediated rejection episode.

Mixed lymphocyte reaction

Intervention Type: DIAGNOSTIC_TEST

Assessment of alloreactive T cell repertoire

Interventions

Mixed lymphocyte reaction

Assessment of alloreactive T cell repertoire

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Kidney transplantation in our center

Exclusion Criteria

• Donor not evaluated by our center

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Rainer Oberbauer

Prof. Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rainer Oberbauer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical university of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Constantin N Aschauer, MD

Role: CONTACT

constantin.aschauer@meduniwien.ac.at

00434040043890

Facility Contacts

Constantin N Aschauer, MD

Role: primary

constantin.aschauer@meduniwien.ac.at

00434040043890

References

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.

Reference Type: DERIVED

PMID: 34721420 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31477052 (View on PubMed)

Other Identifiers

ALL-T-COPIES

Identifier Type: -

Identifier Source: org_study_id