Early Diagnosis of Acute Lung Transplant Rejection

DESCRIPTION (provided by applicant): Lung transplant recipients are at high risk for acute organ rejection, especially during the first three months post-surgery. Presymptomatic diagnosis of this condition is critical for early and effective therapeutic intervention; once overt clinical symptoms indicative of transplant rejection develop, the process is usually well under way and significant lung damage may have already occurred. Standard medical practice relies heavily on serial bronchoscopies and transbronchial biopsies, two highly invasive and uncomfortable procedures which must be performed many times during the course of follow-up care. What is needed is a minimally invasive diagnostic system that can identify acute rejection in its early stages. Source Precision Medicine has performed extensive work on gene expression profiles in normals and in patients with inflammation- and immune-related diseases and has developed a system for high-precision molecular analysis that can be performed in small quantities of whole blood. The objective of Phase I is to evaluate the specific diagnostic potential of a panel of candidate gene loci. The specific aims of the proposed research are to: 1.) Measure the expression of 88 inflammation-immune related genes in whole blood from patients who are about to initiate high-dose immunosuppressive therapy for the treatment of an episode of acute LTx rejection; 2.) compare these data to reference databases of normals and to the patients, themselves, prior to the onset of rejection; and 3.) select a subset of these 88 genes coupled with candidate biomedical algorithms for use in future studies designed to test the ability to predict and monitor acute LTx using the TheraTrax system. The overall objective of this research is to develop a commercial analytical tool for early detection and evaluation of acute organ rejection in lung transplant patients.