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

Abstract EN

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.