Genetics and genomics in human lung transplantation.

Lung transplantation is the only effective treatment for many advanced lung diseases. However, long-term survival after transplantation remains relatively poor, thus limiting the application of lung transplantation to patients with end-stage disease only. Acute and chronic rejection is the main reason for allograft failure. Attempts to treat or prevent rejection have been stymied by our incomplete understanding of the mechanisms leading to this devastating complication and the lack of representative animal models. A systems-biology approach to lung transplantation with the use of genomics and gene expression profiling has led to new insights into the pathogenesis of rejection, by elucidating the mechanisms of T-cell activation and uncovering the role of B cells and innate immunity. Systems-biology approaches, such as genetics and genomics, may allow minimally invasive diagnosis of rejection and permit individually tailored immunosuppressive regimens. Herein we review the emerging application of genomics and genetics to human lung transplantation and highlight the tremendous potential for these approaches to enhance clinical practice and augment our understanding of basic transplant biology.