ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation

NCT03422224 | Unknown

• 1 other identifier: ALL-T-COPIES
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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. 1.Identification of donor-specific T cell receptor sequences pre- and post-transplant by in vitro expansion to determine unique patterns
2. 2.Quantification and comparison of donor-specific T cell clones in kidney biopsy and blood samples.
3. 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. 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Rejection

  biopsy proven rejection

  12 months

Study Arms (2)

Good transplant function

Kidney transplant recipients without histological signs of rejection.

Diagnostic Test: Mixed lymphocyte reaction

Transplant Rejection

Kidney transplant recipinets experiencing a T cell mediated rejection episode.

Diagnostic Test: Mixed lymphocyte reaction

Interventions

Mixed lymphocyte reaction DIAGNOSTIC_TEST

Assessment of alloreactive T cell repertoire

Good transplant function; Transplant Rejection

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Chronic kidney disease

You may qualify if:

• Kidney transplantation in our center

You may not qualify if:

• Donor not evaluated by our center

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical university of Vienna

Vienna, 1090, Austria

RECRUITING

Related Publications (2)

• 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.

  PMID: 34721420 DERIVED

• 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.

  PMID: 31477052 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

PBMC needle biopsy

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Lymphocyte Culture Test, Mixed

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Histocompatibility Testing; Immunologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Immunologic Techniques

Study Officials

• Rainer Oberbauer, MD, PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Constantin N Aschauer, MD

CONTACT

00434040043890; constantin.aschauer@meduniwien.ac.at

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 5, 2018
• Study Start: July 1, 2017
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: October 23, 2023

Record last verified: 2023-10

Locations

AU (1)