title: 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.
authors.affiliation: Division of Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Khurram
authors.initials: K
authors.lastname: Shahzad
authors.forename: Martin
authors.initials: M
authors.lastname: Cadeiras
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Memon
authors.forename: Barry
authors.initials: B
authors.lastname: Zeeberg
authors.forename: Tod
authors.initials: T
authors.lastname: Klingler
authors.forename: Anshu
authors.initials: A
authors.lastname: Sinha
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Tabak
authors.forename: Sreevalsa
authors.initials: S
authors.lastname: Unniachan
authors.forename: Mario C
authors.initials: MC
authors.lastname: Deng