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

Abstract

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. We hypothesized that PBMC gene expression profiles (GEP) can identify patients at risk of CAV. Methods. We retrospectively analyzed a limited set of whole-genome PBMC microarrays from 10 post-transplant patients who did (n = 3) or did not (n = 7) develop advanced grade CAV during their long-term follow-up. We used significance analysis of microarrays to identify differentially expressed genes and High-Throughput GoMiner to assess gene ontology (GO) categories. We corroborated our findings by retrospective analysis of PBMC real-time PCR data from 33 patients. Results. Over 300 genes were differentially expressed (FDR < 5%), and 18 GO-categories including “macrophage activation”, “Interleukin-6 pathway”, “NF-KappaB cascade”, and “response to virus” were enriched by these genes (FDR < 5%). Out of 8 transcripts available for RT-PCR analysis, we confirmed 6 transcripts (75.0%) including FPRL1, S100A9, CXCL10, PRO1073, and MMP9 (P < .05). Conclusion. Our pilot data suggest that GEP of PBMC may become a valuable tool in the evaluation of patients at risk of CAV. Larger prospectively designed studies are needed to corroborate our hypothesis.