Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study
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Published on: April 14, 2010
Benard W Kulohoma1, Fiona Marriage2, Olga Vasieva3
1Centre for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya.
Insights
Invasive pneumococcal disease (IPD) in children shows altered gene expression related to inflammation and immune response. Survivors of IPD exhibit distinct gene expression profiles compared to non-survivors.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- Invasive pneumococcal disease (IPD) caused by *Streptococcus pneumoniae* is a significant global health concern, particularly for HIV-infected children, leading to high morbidity and mortality.
- Understanding the host's inflammatory response is crucial for improving outcomes in pediatric IPD.
Purpose of the Study:
- To compare peripheral blood gene expression profiles in children with pneumococcal meningitis, differentiating between HIV-infected and uninfected cases, and controls.
- To identify gene expression differences between survivors and non-survivors of IPD to understand factors contributing to poorer outcomes.
Main Methods:
- A prospective case-control observational study was conducted in Malawi.
- Gene expression profiling was performed using Affymetrix arrays and validated with RT-qPCR in a cohort of children with IPD and controls.
- Pathway analysis was employed to investigate differentially expressed genes.
Main Results:
- Children with IPD, regardless of HIV status, exhibited significant upregulation of genes involved in immune activation, oxidative stress, and inflammation compared to controls.
- No significant differences in gene expression were observed between HIV-infected and HIV-uninfected IPD cases.
- Survivors showed upregulation of folate receptor 3 (FOLR3) and S100 calcium-binding protein A12 (S100A12) compared to non-survivors.
Conclusions:
- Pediatric IPD is characterized by distinct gene expression patterns related to immune activation, oxidative stress, leukocyte dynamics, and metabolic pathways.
- Gene expression differences, particularly in S100A12, may be associated with survival outcomes in children with IPD.
Introduction:
Invasive pneumococcal disease (IPD), caused by Streptococcus pneumoniae, is a leading cause of pneumonia, meningitis and septicaemia worldwide, with increased morbidity and mortality in HIV-infected children.
Objectives:
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.
Design And Setting:
Prospective case-control observational study in a tertiary hospital in Malawi.
Participants:
Children aged 2 months to 16 years with pneumococcal meningitis or pneumonia.
Methods:
We used the human genome HGU133A Affymetrix array 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 (RT-qPCR) in an independent set of cases with IPD (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.
Conclusion:
Children with IPD demonstrated increased expression in genes regulating immune activation, oxidative stress, leucocyte adhesion and migration, arginine metabolism, and glucocorticoid receptor signalling.
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