Expression Profiling of Human Donor Lungs to Understand Primary Graft Dysfunction After Lung Transplantation

Abstract

Lung transplantation is the treatment of choice for end‐stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10–20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15–25% fail due to primary graft dysfunction (PGD). This has spawned efforts to re‐examine the current selection criteria as well as search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress‐activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD. Lung transplantation is the treatment of choice for end‐stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10–20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15–25% fail due to primary graft dysfunction (PGD). This has spawned efforts to re‐examine the current selection criteria as well as search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress‐activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD.