Cell-based Assays for Antibody-mediated Transplant Rejection

Validating Cell-based Assays for ABMR After Renal Transplantation

Goal: The goal of this study is to validate blood tests, which can detect antibody-mediated rejection (ABMR) after renal transplantation. These cell based assays measure CD154-expressing alloantigen-specific B-cells and their subsets in peripheral blood of adult renal transplant recipients. Thirty recipients will be enrolled at two transplant centers, 10 each with ABMR, T-cell mediated rejection (TCMR), and no rejection. Each subject will be sample twice, before and after rejection. Donor-specific anti-HLA antibodies will also be measured with single antigen beads.

Study Overview

• Status: Unknown
• Conditions: Antibody-Mediated Graft Rejection
• Intervention / Treatment: Diagnostic test: Alloantigen-specific B-cells

Detailed Description

This cross-sectional open label study will evaluate whether alloantigen-specific B-cells and their subsets which express CD154 are associated with antibody-mediated rejection after first time renal transplantation in adult recipients.

Control groups include adult renal transplant recipients with T-cell-mediated rejection, and without rejection of any type.

Alloantigen-specific B-cells will be measured after stimulation of recipient peripheral blood leukocytes with those from corresponding donor and HLA-non-identical reference cells.

Thirty total subjects will be enrolled after IRB-approved informed consent, 15 at each of two sites. These subjects will include ten each with biopsy-proven ABMR and TCMR and ten with no rejection.

Each subject will be sampled twice, before and after treatment rejection, at intervals no less than 30 days, and not to exceed 90 days.

B-cells subsets will include those that also express cytokines, and those that are categorized as memory or naive, and their isotope switched or unswitched subsets, transitional B-cells or plasmablasts, etc.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14215
      • Not yet recruiting
      • Erie County Medical Center
      • Contact: Liise Kayler, MD; Phone Number: 716-361-8500; Email: LKayler@ecmc.edu
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Rohan Vinayak; Email: rohanv@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults who have received primary renal transplants

Description

Inclusion Criteria:

• IRB-approved informed consent.
• Adults (>18 yr to 70 years)
• Primary renal transplant recipients with biopsy-proven ABMR, TCMR or recipients with no rejection

Exclusion Criteria:

• Lack of informed consent
• Concomitant BK virus infection
• Vulnerable populations including children <18 yr, pregnant women, and prisoners

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ABMR; Biopsy-proven ABMR-Banff criteria, with or without Complement binding donor-specific anti-HLA antibodies	Diagnostic test: Alloantigen-specific B-cells; Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry
TCMR; Biopsy-proven TCMR-Banff 1A, 1B, 2 and 3	Diagnostic test: Alloantigen-specific B-cells; Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry
No Rejection; Biopsy-proven, or clinical criteria	Diagnostic test: Alloantigen-specific B-cells; Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody-mediated rejection	Biopsy-proven antibody-mediated rejection after primary renal transplantation	up to 90 days per subject

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T-cell mediated rejection (TCMR)	Biopsy-proven TCMR after primary renal transplantation	up to 90 days per subject

Collaborators and Investigators

• Sponsor: Plexision
• Collaborators: Medical University of South Carolina
• Investigators: Study Director: Rakesh Sindhi, MD, Plexision

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Anticipated): June 14, 2021
• Study Completion (Anticipated): August 14, 2021

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Renal Transplantation; Adults; B-cells; CD154; Antibody mediated Rejection; B-cell subsets; alloantigen-specific
• Other Study ID Numbers: 00033434

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be retained at enrollment sites, Results of testing samples, and related de-identified data of the subject will be summarized and shared with all investigators of this study, and reported in publications

Drug and device information, study documents

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