# Measuring the Impact of Allosensitization on Xenotransplantation

> **NIH NIH R21** · DUKE UNIVERSITY · 2021 · $201,250

## Abstract

Antibody-mediated rejection (AMR) is a barrier to successful long-term xenograft survival. We compared AMR
in kidney xenotransplantation to sensitized kidney allotransplantation in a NHP model. With conventional CNI-
based immunosuppressive maintenance, both groups showed limited graft survival with strong AMR features
such as interstitial hemorrhage, thrombotic microangiopathy, peritubular capillaritis, and glomerulitis without T
cell mediated rejection. The strong similarity between sensitized allo- and unsensitized xeno-rejection suggests
a possible common mechanism of rejection in xeno- and sensitized allotransplantation. Currently pig to primate
graft survival has markedly improved with interruption of the CD28/B7 and CD40/CD154 costimulation
pathways. In theory, the same regimen should control the immune response against xenografts in
allosensitized animals. Therefore, further investigation is warranted to evaluate the current successful
costimulation blockade-based regimen that has shown great efficacy in xenotransplantation to determine if this
strategy may apply as well to sensitized recipients.

## Key facts

- **NIH application ID:** 10126807
- **Project number:** 5R21AI151398-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Stuart Johnston Knechtle
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2020-03-12 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126807

## Citation

> US National Institutes of Health, RePORTER application 10126807, Measuring the Impact of Allosensitization on Xenotransplantation (5R21AI151398-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10126807. Licensed CC0.

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