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Published on: October 31, 2025
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Peripheral Blood Gene Expression Changes Associated With Primary Graft Dysfunction After Lung Transplantation.
J M Diamond1, E Cantu2, M K Porteous1
1Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Summary
Gene expression in peripheral blood differs in lung transplant recipients with primary graft dysfunction (PGD). These immune gene expression changes occur early after transplant and may impact allograft survival.
Area of Science:
- Immunology
- Transplantation Biology
- Genomics
Background:
- Primary graft dysfunction (PGD) is a significant complication following lung transplantation.
- Recipient immune responses to the allograft are critical for transplant success.
- Understanding early molecular events in PGD is crucial for improving outcomes.
Purpose of the Study:
- To investigate longitudinal differences in peripheral blood gene expression in lung transplant recipients with and without PGD.
- To identify specific genes and pathways associated with PGD development.
- To determine the temporal dynamics of gene expression changes related to PGD.
Main Methods:
- Peripheral blood RNA expression was measured in 106 lung transplant recipients over the first post-transplant year.
- A panel of 100 hypothesis-driven genes was analyzed.
- PGD was defined as grade 3 within 72 hours post-transplant.
Main Results:
- Eighteen genes showed differential expression over the first year in relation to PGD.
- Sixteen genes, primarily related to innate immunity and inflammasome pathways, were overexpressed within 7 days in PGD patients.
- Thirteen genes, including T cell and adaptive immune regulation genes, were underexpressed within 7 days in PGD patients.
- Gene expression differences were detectable as early as 2 hours post-reperfusion.
Conclusions:
- Peripheral blood gene expression profiles, particularly involving innate and adaptive immunity, are altered in lung transplant recipients experiencing PGD.
- These molecular signatures emerge very early after transplantation, within hours of reperfusion.
- Further research is warranted to explore the long-term prognostic value of these early gene expression changes for allograft fate.
