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Microarray investigation of host RNA expression profiles in neonatal infection

Presented at the Neonatal Society 2010 Summer Meeting (programme).

Smith CL1,3, Dickinson P1, Craigon M1, Ross A1, Khondoker MR1, Forster T1, Ivens A2, Jackson A3, Lacaze P1, Stenson BJ3, Ghazal P1

1 Division of Pathway Medicine, University of Edinburgh, UK
2 FIOS Genomics, University of Edinburgh, UK
3 Neonatal Unit, Royal Infirmary of Edinburgh, UK

Aim: To examine differences in host RNA expression profiles between infants with confirmed infection and control infants using microarray technology.

Background: Infection causes significant morbidity and mortality in newborn infants. Currently available methods for diagnosing infection are unreliable. We aimed to investigate whether alterations in neonatal host RNA patterns in response to infection can be detected 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 (1). 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. Ethical approval was obtained for this study.

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.

Conclusion: There is clear immune-related differential gene expression between infected and control infants. 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 will be able to be defined.

1. CL Smith et al. Analyst 2007; 132: 1200-1209

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