RNA Analysis Can Identify Rejection In Lung Transplant Recipient

By distinguishing the patterns of gene expression in white blood cells (leukocytes), which fluctuate during the rejection of foreign tissue, PCR-based gene profiling can identify individual genes and pathways associated with the rejection status of transplanted lungs. In addition, the study shows that some of the genes whose expression changes during rejection of a transplanted lung are the same as those whose expression changes during the rejection of a transplanted heart.

Using microarray analysis, the researchers identified 259 genes that were differentially expressed for A0 and >A2 rejection grades (based on a standardized severity scale of 0-4). RT-PCR confirmed 14 of these genes as candidates for analysis, revealing a high correlation with those identified using microarray analysis. Seven of those genes were considered statistically significant.

"We are excited to confirm that new monitoring methods, such as non-invasive blood tests that determine a patient's gene expression profile, can identify those genes that are expressed during the rejection of a lung," said Dr. Keshavjee. "The data being presented at this year's ISHLT meeting shows the potential that exists to develop a non-invasive test that could alleviate the need for tens of thousands of biopsies."

Currently, uncomfortable and invasive biopsies are the standard for monitoring lung transplant recipients for acute cellular rejection. Biopsies are performed frequently in the first year post-transplant and periodically thereafter, often for the patient's lifetime.

Current data shows that 1,400 lung transplants were performed in 2006. And in recent years, approximately 83.3 percent of lung transplant patients survived one year following the transplant, while 62.8 percent survived three years and 47.3 survived five years. Transplant rejection is a primary concern for long-term survival, both immediately after surgery and through the patient's lifetime. To prevent rejection and subsequent damage to the new lungs, patients must take a lifelong regimen of immunosuppressive drugs.

About the LARGO Study

The LARGO Study was presented  by Shaf Keshavjee, M.D., Chair, Division of Thoracic Surgery, University of Toronto, and LARGO study lead, at the 27th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT).

The  study was initiated in April 2004 to examine the utility of molecular testing in post-transplant lung patient management. Fourteen centers from five countries and two continents are participating in this study to investigate the utility of gene expression testing for management of lung transplant recipients.

Several thousand samples have been collected in the LARGO database. The LARGO study and database provide an unparalleled resource for genomic and molecular diagnostic studies and development in lung transplantation. The studies presented at ISHLT were sponsored by XDx, whose laboratory provides the gene expression testing service used in the investigation.