Peripheral blood mononuclear cell transcriptome profiles suggest T-cell immunosuppression after uncomplicated mechanical circulatory support device surgery

Abstract

Mechanical circulatory support device (MCSD) surgery in patients with advanced heart failure patients is often complicated by infections that are linked to altered cell-mediated immunity. Using a transcriptome-wide peripheral blood mononuclear cell (PBMC) gene expression profiling approach, we analyzed expression patterns directly before and after MCSD implantation in 11 patients who had an uncomplicated course after MCSD implantation (Day 0-24 hours before, Day 1-24 hours after, and Day 7-1 week after implantation). Data were analyzed using Significance Analysis of Microarrays (SAM) and High-Throughput GoMiner on post-implantation profiles (Day 1, Day 7) in comparison with baseline (Day 0). Day1 profiles included differential expression of 821 genes (SAM, FDR <0.1, fold change >1.5), enriching >60 Gene Ontology (GO) categories. Grouping by component genes revealed GO clusters, which we term “interleukin related” (primarily upregulated), “T-cell related” (primarily downregulated), and “apoptosis related” (both up- and down-regulated genes). Day 7 profiles included GO categories related to repair processes. In conclusion, transcriptome-wide expression profiling of PBMCs suggests a response pattern to MCSD implantation of inflammatory activation and simultaneous T-cell suppression.