Dataset Information

The blood transcriptome of childhood malaria.

ABSTRACT: BACKGROUND:Transcriptomic research of blood cell lineages supports the understanding of distinct features of the immunopathology in human malaria. METHODS:We used microarray hybridization, validated by real-time RT-PCR to analyze whole blood gene expression in healthy Gabonese children and children with various conditions of Plasmodium falciparum infection, including i) asymptomatic infection, ii) uncomplicated malaria, iii) malaria associated with severe anemia and iv) cerebral malaria. FINDINGS:Our data indicate that the expression profile of 22 genes significantly differed among the investigated groups. Immunoglobulin production, complement regulation and IFN beta signaling, in particular IRF7 and ISRE binding signatures in the corresponding genes, were most conspicuous. Down-regulation in cerebral malaria seems to rely on AhRF, GABP and HIF1 hypoxia transcription factors. ARG1, BPI, CD163, IFI27, HP and TNFAIP6 transcript levels correlated positively with lactatemia, and negatively with hemoglobin concentrations. INTERPRETATION:Differences in gene expression profile reflect distinct immunopathological mechanisms of P. falciparum infection. They emerge as potential prognostic markers for early therapeutic measures and need to be validated further. FUND: This work was supported by a grant of the NGFN (Nationales Genomforschungsnetz 01GS0114) and by a CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) PhD scholarship for A. B. W. Boldt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

SUBMITTER: Boldt ABW

PROVIDER: S-EPMC6412103 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The blood transcriptome of childhood malaria.

Boldt Angelica B W ABW van Tong Hoang H Grobusch Martin P MP Kalmbach Yvonne Y Dzeing Ella Arnaud A Kombila Maryvonne M Meyer Christian G CG Kun Jürgen F J JFJ Kremsner Peter G PG Velavan Thirumalaisamy P TP

EBioMedicine 20190110

<h4>Background</h4>Transcriptomic research of blood cell lineages supports the understanding of distinct features of the immunopathology in human malaria.<h4>Methods</h4>We used microarray hybridization, validated by real-time RT-PCR to analyze whole blood gene expression in healthy Gabonese children and children with various conditions of Plasmodium falciparum infection, including i) asymptomatic infection, ii) uncomplicated malaria, iii) malaria associated with severe anemia and iv) cerebral m ...[more]

PMID: 30638864

Similar Datasets

Project description:We aimed at finding differently expressed genes in whole blood cells of African children with asymptomatic Plasmodium falciparum infection (A), uncomplicated malaria (U), severe malarial anemia (A) and cerebral malaria (Ce) compared one to another and to healthy children (Co). Understanding malarial immunopathology in the human host represents and enormous challenge for transcriptomic research. In this work, we used microarray and real-time RT-PCR technology to pursue deeper knowledge about the mechanisms underlying this disease in African children. To this end, we investigated the genomic transcriptional profiles in whole blood of healthy children and children with asymptomatic infection, uncomplicated malaria, malaria associated with severe anemia and cerebral malaria and compared them with previously published microarray results. We were able to discriminate between the different presentations of P. falciparum infection using supervised and unsupervised clustering of microarray data and unsupervised double-hierarchical clustering of real-time RT-PCR results of a set of 22 genes known to be expressed in at least one of the principal blood cell lineages. We further found considerable overlap between genes regulated in Kenyan and Gabonese children with symptomatic malaria, in contrast to adults with acute malaria from Cameroon. Different signatures for transcription factor binding sites in promoters of genes either up-regulated in symptomatic disease, specifically up-regulated in uncomplicated malaria or specifically down-regulated in cerebral malaria point out that similar gene expression in each of these clinical presentations is probably a result of common regulation at the transcriptional level. Immunoglobulin production, complement regulation and IFN beta signalling emerged as most discrepant features between uncomplicated malaria and all other investigated presentations, correlating with IRF7 and ISRE binding signatures in the corresponding genes. Down-regulation of several genes in cerebral malaria seems instead to be a response to hypoxia orchestrated by AhRF, GABP and HIF1 transcription factors. ARG1, BPI, CD163, IFI27, HP and TNFAIP6 transcript levels correlated positively with lactatemia and inversely with hemoglobin concentration and should be evaluated as prognostic markers to direct early therapeutic measures and prevent malarial disease evolution and death.

Project description:BackgroundAsthma is a chronic disorder of both adults and children affecting more than 300 million people heath worldwide. Diagnose and treatment for asthma, particularly in childhood asthma have always remained a great challenge because of its complex pathogenesis and multiple triggers, such as allergen, viral infection, tobacco smoke, dust, etc. It is thereby great significant to deeply investigate the transcriptome changes in asthmatic children before and after desensitization treatment, in order that we could identify potential and key mRNAs and lncRNAs which might be considered as useful RNA molecules for observing and supervising desensitization therapy for asthma, which might guide the diagnose and therapy in childhood asthma.MethodsIn the present study, we performed a systematic transcriptome analysis based on the deep RNA sequencing of ten asthmatic children before and after desensitization treatment, including identification of lncRNAs using a stringent filtering pipeline, differential expression analysis and network analysis, etc. RESULTS: First, a large number of lncRNAs were identified and characterized. Then differential expression analysis revealed 39 mRNAs and 15 lncRNAs significantly differentially expressed which involved in two biological processes and pathways. A co-expressed network analysis figured out a desensitization-treatment-related module which contains 27 mRNAs and 21 lncRNAs using WGCNA R package. Module analysis disclosed 17 genes associated to asthma at distinct level. Subsequent network analysis based on PCC figured out several key lncRNAs probably interacted to those key asthma-related genes, i.e., LINC02145, GUSBP2. Our functional investigation indicated that their functions might involve in immune, inflammatory response and apoptosis process.ConclusionsOur study successfully discovered many key noncoding RNA molecules related to pathogenesis of asthma and relevant treatment, which may provide some clues for asthmatic diagnose and therapy in future.

Project description:BACKGROUND:Red blood cell variants protect African children from severe falciparum malaria. However, their individual and interactive effects on mild disease and parasite density, and their modification by age-dependent immunity, are poorly understood. In this study, we address these knowledge gaps in a prospective cohort study of malaria risk and Plasmodium falciparum densities in Malian children. METHODS:The Kenieroba Innate Defense Study for Malaria (KIDS-Malaria) was a 4-year prospective cohort study of children aged 6 months to 17 years undertaken in Mali between 2008 and 2011. Red blood cell variants were haemoglobin S (HbS), haemoglobin C (HbC), ? thalassaemia, ABO blood groups, and glucose-6-phosphate dehydrogenase (G6PD) deficiency encoded by the X-linked A- allele. The primary outcome was malaria incidence, measured as the number of uncomplicated or severe malaria episodes over time. The secondary outcome was parasite density at the time of a malaria episode. We modelled incidence rate ratios with quasi-Poisson regression and we analysed parasite densities using generalised estimating equations. This study is registered with ClinicalTrials.gov, number NCT00669084. FINDINGS:Between May 1, 2008, and Dec 29, 2011, we enrolled 1586 children into the study. We successfully typed all five red blood cell variants for 1543 of these children, who therefore constituted the evaluable population and in whom we diagnosed 4091 malaria episodes over 2656 child-years of follow-up. In these 1543 children, red blood cell variants were common, and occurred at the following frequencies: sickle cell trait (HbAS) 220 (14%), HbC heterozygosity (HbAC) 103 (7%), ? thalassaemia 438 (28%), type O blood group 621 (40%), and G6PD deficiency 72 (9%) in 767 boys and 158 (20%) in 776 girls. The overall incidence of malaria was 1.54 episodes per child-year of follow-up, ranging from 2.78 episodes per child-year at age 3 years to 0.40 episodes per child-year at age 17 years. The malaria incidence was lower in HbAS children than in HbAA children with normal haemoglobin (adjusted incidence rate ratio [aIRR] 0.66 [95% CI 0.59-0.75], p<0.0001) and lower in G6PD A-/A- homozygous girls than in G6PD A+/A+ girls (0.51 [0.29-0.90], p=0.020), but was higher in HbAC children than in HbAA children (1.15 [1.01-1.32], p=0.039). Parasite density was lower in HbAS children (median 10,550 parasites per ?L [IQR 1350-26,250]) than in HbAA children (15,150 parasites per ?L [4250-31,050]; p=0.0004). The HbAS-associated reductions in malaria risk and parasite density were greatest in early childhood. INTERPRETATION:The individual and interactive effects of HbAS, HbAC, and G6PD A-/A- genotypes on malaria risk and parasite density define clinical and cellular correlates of protection. Further identification of the molecular mechanisms of these protective effects might uncover new targets for intervention. FUNDING:Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Dataset Information

The blood transcriptome of childhood malaria.

Publications

The blood transcriptome of childhood malaria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets