Gene Expression Signatures of Peripheral Blood Mononuclear Cells during the Early Post-Transplant Period in Patients Developing Cardiac Allograft Vasculopathy.

Background. Cardiac allograft vasculopathy (CAV) is a major cause of graft loss and death after heart transplantation. Currently, no diagnostic methods are available during the early post-transplant period to accurately identify patients at risk of CAV.

Drawing networks of rejection - a systems biological approach to the identification of candidate genes in heart transplantation.

Technological development led to an increased interest in systems biological approaches to characterize disease mechanisms and candidate genes relevant to specific diseases. We suggested that the human peripheral blood mononuclear cells (PBMC) network can be delineated by cellular reconstruction to guide identification of candidate genes. Based on 285 microarrays (7370 genes) from 98 heart transplant patients enrolled in the Cardiac Allograft Rejection Gene Expression Observational study, we used an information-theoretic, reverse-engineering algorithm called ARACNe (algorithm for the reconstruction of accurate cellular networks) and chromatin immunoprecipitation assay to reconstruct and validate a putative gene PBMC interaction network.

Clinical implications and longitudinal alteration of peripheral blood transcriptional signals indicative of future cardiac allograft rejection.

Background: We have previously demonstrated that a peripheral blood transcriptional profile using 11 distinct genes predicts onset of cardiac allograft rejection weeks to months prior to the actual event.

Methods: In this analysis, we ascertained the performance of this transcriptional algorithm in a Bayesian representative population: 28 cardiac transplant recipients who progressed to moderate to severe rejection; 53 who progressed to mild rejection; and 46 who remained rejection-free. Furthermore, we characterized longitudinal alterations in the transcriptional gene expression profile before, during and after recovery from rejection.

Gene expression profiling distinguishes a molecular signature for grade 1B mild acute cellular rejection in cardiac allograft recipients.

Background: Gene expression profiling distinguishes the absence or presence of moderate to severe grades of acute cellular rejection in cardiac allograft recipients using a 20-gene classifier. We explored the hypothesis that the rejection classifier also differentiates various forms of mild rejection and we performed sub-analyses based on time post-transplant and confirmatory pathology interpretations.

Methods: A post hoc analysis of 265 CARGO study patients and 714 clinical encounters focused on the correlation of rejection classifier-derived gene expression (GE) scores for blood samples accompanying endomyocardial biopsies.

Transcriptional signals of T-cell and corticosteroid-sensitive genes are associated with future acute cellular rejection in cardiac allografts.

Background: Profiling mRNA levels of 11 informative genes expressed by circulating immune effector cells identifies cardiac allograft recipients at low risk for current moderate-severe acute cellular rejection (ACR).

Methods: We conducted a nested case-control study of 104 cardiac allograft recipients to investigate the association of transcriptional profiles of blood samples with either a future rejection episode within 12 weeks of a baseline clinical sample or persistent histologic quiescence for the same time period.

Results: The transcription profile yielded a score (0 to 40 scale) of 27.