# The Role of Telomeres in Lung Transplant Recipient Immunity and Outcomes

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $697,995

## Abstract

Project Summary
Lung transplantation (LTx) is the only therapeutic option for patients with end-stage lung disease and idiopathic
pulmonary fibrosis (IPF) is the most common indication in North America. However, IPF lung transplant recipients
(IPF-LTRs) have worse transplant survival compared to all other lung diseases. Mutations in the genes
responsible for telomere maintenance are the most common identifiable cause of IPF and our group recently
showed that lung transplantation enriches for patients with telomere-mediated disease with as many as a quarter
of patients having an identifiable rare variant. Patients with defects in telomere-maintenance genes have an
array of immunologic abnormalities that render them susceptible to viral infections. Despite having a weakened
immune system, these patients have been reported to reject donor lungs at similar or faster rates than individuals
without telomere-mediated disease. The mechanism responsible for this phenomenon are unknown. Based on
our preliminary data, we hypothesize that lung transplantation unmasks a complex syndrome that impacts viral
host defense, immunosuppression tolerance and allograft rejection. Further, we hypothesize that impaired
adaptive immunity is exacerbated by Cytomegalovirus infection by augmenting immunosenescence, however
alloimmune and other immune mechanisms can offset and facilitate lung rejection outcomes in transplant
recipients with short telomeres. We have divided our approach into three related and synergistic aims. In Aim 1,
we examine the consequences of primary CMV infection in patients with telomere-mediate disease and test if
two hits, telomere dysfunction and CMV infection, cooperate to drive immune senescence. In Aim 2, we explore
the mechanisms that are responsible for lung rejection in individuals with weakened immune systems. Finally,
in Aim 3, we test if our recent findings from the University of Pittsburgh can be replicated and extended in a multi-
center group of patients from the Lung Transplant Outcomes Group and examine keep outcomes following lung
transplantation when stratified by genetic findings and telomere length. We expect that these studies will help
improve care and outcomes in patients with telomere-mediated disease.

## Key facts

- **NIH application ID:** 10802188
- **Project number:** 5R01HL166265-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Jonathan K. Alder
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $697,995
- **Award type:** 5
- **Project period:** 2023-03-05 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802188

## Citation

> US National Institutes of Health, RePORTER application 10802188, The Role of Telomeres in Lung Transplant Recipient Immunity and Outcomes (5R01HL166265-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10802188. Licensed CC0.

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