Gene Expression Profiling: A Great Advance in Detecting Graft Rejection

By René J. Alvarez, Jr., MD, FACC, FAHA

GeneX_v2_sgalvarezMuch of our success with heart transplantation in the past half-century has been attributable to advances in immuno-suppression. However, acute cellular rejection is still an issue, especially in the first year after a transplant. Rejection is associated with graft failure and graft loss, as well as long-term sequelae. Endomyocardial biopsy remains the gold standard in the surveillance of rejection but is associated with procedural risks and patient discomfort.

Fortunately, better understanding of the immune system has led to a validated, non-invasive method of detecting rejection: gene expression profiling (GEP). This involves the quantitative assessment of mononuclear cell gene expression from peripheral blood. GEP is based on the analysis of peripheral blood mononuclear cell RNA with an algorithm that utilizes 20 genes (11 informative, 9 controls) as a means of detecting rejection. Unlike an endomyocardial biopsy, this technique requires only a blood sample. GEP has been shown to be a safe way to help detect rejection and guide immunosuppression.

Soon we will celebrate the 50th anniversary of the first human heart transplant, an exceptional human achievement that has saved the lives of thousands of people. Yet even now, our understanding of the immune system and molecular biology continue to evolve and yield new benefits for clinical practice.