Peripheral blood RNA gene expression profiling in the patients with community-acquired bacterial meningitis

Abstract

Objectives: We aimed to describe the genetic pathways activated during the community acquired bacterial meningitis (BM) and healthy controls by using genome-wide RNA expression profiling combined with functional annotation of transcritpional changes. S518 20th ECCMID, Posters Study was performed in 21 patients with BM and their data were compared with eighteen age and sex matched healthy controls. Methods: We included 21 patients (median age 56.1 years) with culture proven BM hospitalised between the 1st of January and 31st of December 2008. The control group consisted of 18 age and sex matched subjects (median age 55.3 years). The blood samples were collected via venepuncture on admission. The RNA was extracted from whole blood, a and b globin mRNA was depleted and gene expression profiling was performed with GeneChip Human Gene 1.0 ST Arrays (Affymetrix, Santa Clara, USA) enabling the analysis of 28,869 genes. To verify the genechip results, we chose ten genes (CD177, IL1R2, IL18R1, IL18RAP, OLFM4, TLR5, CPA3, FCER1A, IL5RA, IL7R) from the gene expression profiling data and performed further analyse with real-time (RT) PCR. Quantitative RT-PCR successfully verified previously found differences. Gene expression profile data was analysed by Bayesian modelling. To define changed genetic networks functional annotation of enriched gene sets was used. Results: BM was mainly caused by Streptococcus pneumonia (14) followed by Neisseria meningitidis (2) and Streptococcus agalactiae (2). Comparing the controls with the patients, we identified the significant changes at p values of <0.05 in 8569 genes, after False Discovery Rate (FDR) correction total of 5500 genes remained significant at p value of <0.01. Functional annotation and network analysis indicated that most of the genes were related to activation of inflammatory processes. Next common of the upregulated genes were responsible for allergic reactions and anaphylaxia. Those changes were seen in our study both among the adults and the children. Conclusion: This study demonstrates a strong functional evidence of the activated immune response. This may indicate that the protective reactions caused by severe and active infection are even too strong