Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study.
BMJ Paediatr Open
; 1(1): e000092, 2017.
Article
em En
| MEDLINE
| ID: mdl-29637127
ABSTRACT
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 ANDSETTING:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Observational_studies
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article