80 Microarray Investigation of Host Rna Expression Profiles in Neonatal Infection

Abstract

Background and aims: Infection causes significant neonatal morbidity and mortality. Currently available methods for diagnosing infection are unreliable. We aimed to examine differences in host RNA expression profiles between infants with confirmed infection and control infants using microarray technology. Methods: RNA was extracted from neonatal whole blood taken from infants with confirmed infection and from controls using a modified PAXgene™ Blood RNA system protocol. High quality RNA was run on Illumina® Human Whole-Genome Expression BeadChip microarrays. Normalised, validated microarray data was analysed to examine differences between control and infected samples. Functional annotation according to gene ontology and pathway analysis was performed. Results: 28 infected and 35 control samples were examined. Differential gene expression between infected and control groups was analysed: 448 features had >2-fold up-regulation and 341 features >2-fold down-regulation (p< 0.001) in infected compared to control infants. There was significant immune-related differential gene expression. Up-regulated genes in the infected group included genes involved in cytokine, complement, interferon and Toll Like Receptor related processes. Down-regulated genes included genes involved in antigen processing, MHC II activity and T cell activation and signalling. Conclusions: There is immune-related differential gene expression between infected and control infants. Many of our results corroborate findings previously published for adult and paediatric populations. In addition, these results provide evidence that neonates are capable of mounting a substantial immune response to infection. It is likely that, with larger studies and, with examination of training sets of data, immune gene expression signatures for neonatal infection can be defined