# Exosomes and the Immune Response in Allograft Outcomes in Pediatric Transplant Recipients

> **NIH NIH U01** · STANFORD UNIVERSITY · 2021 · $2,188,844

## Abstract

PROJECT SUMMARY/ABSTRACT PARENT GRANT
Solid organ transplantation is currently the treatment of choice for children with a variety of end-
stage organ diseases. The success of clinical transplantation is dependent on the use of potent
immune-suppressive drugs to prevent rejection of the allograft. However, even with our arsenal
of immune-suppressive agents, between 10-40% of pediatric transplant recipients will have a
rejection episode in the first-year post-transplant. Clearly, acute rejection remains a major
hurdle in pediatric solid organ transplantation and thus is the critical question to be addressed in
the proposed mechanistic study. The CTOT-C “Biomarkers for Post-Transplant
Lymphoproliferative Disorders in Children” will enroll over 1000 pediatric recipients of liver,
heart, kidney or intestinal grafts and thousands of individual blood samples will be collected,
processed (whole blood, PBMC and plasma) and stored at Stanford. In this proposal, the unique
CTOTC-06 cohort of samples, clinical data and established infrastructure will be utilized to
identify novel and robust surrogate endpoints of allograft status. In preliminary studies we have
identified microRNAs and cellular phenotypes that correlate with either acute rejection or stable
graft function. We now propose to determine the exosome miRNome, analyze TCR and
immunoglobulin heavy chain repertoires, and perform a multi-parameter analysis of the
alloimmune response by mass cytometry with the goal of identifying biomarkers of stable graft
function and acute rejection in recipients of liver, heart, kidney and intestine transplants. We
hypothesize that we can identify unique cellular, molecular, and functional changes in the
immune response that are associated with and predictive of graft outcomes. We will test this
hypothesis in the following specific aims:
Aim 1: Determine the impact of an allograft on the early post-transplant immune response.
Aim 2: Establish novel diagnostic and predictive approaches to determine allograft status.
The development of novel and robust surrogate endpoints of allograft status will be a major
advance in the field of pediatric solid organ transplantation.

## Key facts

- **NIH application ID:** 10339207
- **Project number:** 3U01AI135950-03S2
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sheri M. Krams
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,188,844
- **Award type:** 3
- **Project period:** 2021-04-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10339207

## Citation

> US National Institutes of Health, RePORTER application 10339207, Exosomes and the Immune Response in Allograft Outcomes in Pediatric Transplant Recipients (3U01AI135950-03S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10339207. Licensed CC0.

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