Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case control study
Kulohoma BW1, Marriage F2, Vasieva O3, Mankhambo L4, Nguyen K5, Molyneux ME4, Molyneux EM6, Day PJR2, Carrol ED4,5,6 1Centre for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya; 2Centre for Integrated Genomic Research, University of Manchester, Manchester, UK; 3Institute of Integrative Biology, University of Liverpool, Liverpool, UK; 4Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; 5Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; 6Department of Paediatrics, University of Malawi, College of Medicine, Blantyre, Malawi
Background and Aims: Invasive pneumococcal disease (IPD) has increased morbidity and mortality rates among HIV infected children. We aimed to compare peripheral blood expression profiles between HIV infected and uninfected children with pneumococcal meningitis and controls, and between survivors and non-survivors, in order to provide insight into the host inflammatory response leading to poorer outcomes.
Methods: Children aged 2 months to 16 years were enrolled to a prospective case-control observational study in a tertiary hospital in Malawi. The human genome HGU133A Affymetrix array was used to explore differences in gene expression between cases with pneumococcal meningitis (n=12) and controls, and between HIV-infected and uninfected cases, and validated gene expression profiles for 34 genes using real-time quantitative PCR in an independent set of IPD cases (n=229) and controls (n=13). Pathway analysis was used to explore genes differentially expressed.
Results: Irrespective of underlying HIV infection, cases showed significant upregulation compared with controls of the following: S100 calcium-binding protein A12 (S100A12); vanin-1 (VNN1); arginase, liver (ARG1); matrix metallopeptidase 9 (MMP9); annexin A3 (ANXA3); interleukin 1 receptor, type II (IL1R2); CD177 molecule (CD177); endocytic adaptor protein (NUMB) and S100 calcium-binding protein A9 (S100A9), cytoskeleton associated protein 4 (CKAP4); and glycogenin 1 (GYG1). RT-qPCR confirmed differential expression in keeping with microarray results. There was no differential gene expression in HIV-infected compared with HIV uninfected cases, but there was significant upregulation of folate receptor 3 (FOLR3), S100A12 in survivors compared with non-survivors.
Credits: None available.
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