# Role of integrin CD11b in delayed graft function and allorejection

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $203,188

## Abstract

Project Summary/Abstract
Delayed graft function (DGF) is a manifestation of ischemia-reperfusion injury (IRI) in the transplanted kidney
allograft. DGF is an important risk factor in T-cell or antibody-mediated biopsy-proven acute rejection, and the
strongest risk factor for chronic allograft dysfunction, exceeding even that of pre-transplant diabetes. IRI is an
acute inflammatory response mediated by the recipient's activated innate immune cells that infiltrate the
ischemic organ following reperfusion. Previous efforts to limit IRI, conducted primarily in rodents, have targeted
individual proinflammatory mediators and showed promise in rodents, but this approach was less effective in
large animals and failed in human trials. We have demonstrated that the archetypal innate immune receptor
leukocyte integrin CD11b/CD18 mediates IRI in native nonhuman primate (NHP) kidneys, and that a first-in-
class anti-CD11b monoclonal antibody (mAb107) protected IRI native kidneys from otherwise irreversible
kidney failure. The main objective of this exploratory R21 is to evaluate the effect of limiting IRI with mAb107
on DGF in our well-studied NHP kidney transplant model. We have also shown that the recipient's innate
alloreactive memory T cells present in primates but absent in laboratory mice, play a critical role in allograft
rejection. Our preliminary data show that these cells express CD11b, and are inhibited by mAb107 in vitro.
Therefore, a second objective of this study is to evaluate the effect of mAb107 on the proinflammatory
functions of these alloreactive cells in NHP transplant recipients. These studies should help elucidate the
mechanisms linking innate DGF, rejection and allograft outcome, and may help define an effective approach to
limiting the progressive fibrosis currently observed clinically in 65% of renal allografts.

## Key facts

- **NIH application ID:** 9932329
- **Project number:** 5R21AI146871-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** M. AMIN ARNAOUT
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,188
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932329

## Citation

> US National Institutes of Health, RePORTER application 9932329, Role of integrin CD11b in delayed graft function and allorejection (5R21AI146871-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932329. Licensed CC0.

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