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Project description:Blood gene expression profiles of children with wheezing
| PRJNA1095160 | ENA
Project description:Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population. We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n=16; no sensitization, n=36). Blood neutrophils were purified and cultured overnight with polyinosinic:polycytidylic acid (poly(I:C)) as a viral analog stimulus. Neutrophils underwent next-generation sequencing with Reactome pathway analysis and were analyzed for cytokine secretion, apoptosis, myeloperoxidase and extracellular DNA release. CD14+ monocytes were also exposed to neutrophil culture supernatant and analyzed for markers of M1 and M2 activation. 495 genes, related largely to the innate immune system and neutrophil degranulation, were differently expressed in children with versus without aeroallergen sensitization. Functional experiments identified more neutrophil degranulation and extracellular trap formation (i.e., more myeloperoxidase and extracellular DNA) and less neutrophil pro-inflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (i.e., M2) phenotype in sensitized children and a more pro-inflammatory (i.e., M1) phenotype in non-sensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled healthcare were also higher in children without aeroallergen sensitization after enrollment. Systemic neutrophil responses to viral infection differ by allergic phenotype and may be less effective in preschool children without allergic inflammation. Further studies of neutrophil function are needed in this population, which often has less favorable therapeutic responses to inhaled corticosteroids and other therapies directed at T2-high inflammation.
2024-01-29 | GSE254019 | GEO
Project description:Background: Farm exposures in early life reduce the risks for childhood allergic diseases and asthma. There is less information about how farm exposures relate to respiratory illnesses and mucosal immune development. Objective: We hypothesized that children raised in farm environments have a lower incidence of viral illnesses over the first two years of life than non-farm children. We also analyzed between farm exposures or respiratory illnesses were related to patterns of nasal cell gene expression. Methods: The Wisconsin Infant Study Cohort (WISC) birth cohort enrolled farm and non-farm pregnant women from central Wisconsin. Parents reported prenatal farm and other environmental exposures. Illness frequency and severity were assessed using illness diaries and periodic surveys. Nasopharyngeal cell gene expression at age two years was compared to farm exposure and respiratory illness history. Results: There was a higher rate of respiratory illnesses in the non-farm vs. farm group (rate ratio 0.82 [0.69,0.97], p=0.020), but no significant differences in wheezing illnesses. There was a stepwise reduction in rates of respiratory illnesses in children exposed at least weekly to 0, 1, or ≥2 animals (p=0.006). In analyzing nasal cell gene expression, farm exposures and preceding respiratory illnesses were positively related to gene signatures for mononuclear cells and innate and antimicrobial responses. Conclusions: Children exposed to farms and farm animals had lower rates of respiratory illnesses over the first two years of life. Both farm exposures and preceding respiratory illnesses were associated with increased innate immune responses, suggesting that these exposures stimulate mucosal immune responses to reduce subsequent illness frequency.
2024-01-29 | GSE233761 | GEO
Project description:Children develop rapidly during the first years of life, and understanding the different sources and levels of variation in serum proteome of young children is important when using serum proteins as markers for childhood diseases. We have performed label/free quantitative proteomics for longitudinal serum samples collected from a group of children during the first years of life.
2018-04-18 | PXD006775 | Pride
Project description:This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status). Results: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathways analysis identified gene pathways related to inflammation (e.g., dopaminergic and GABAergic synapse pathways). Conclusion: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life.
2021-08-05 | GSE164873 | GEO
Project description:Extensive epigenetic remodelling takes place during early life; however, the alterations of DNA methylation that occur during this period have not been sufficiently addressed by longitudinal studies. We made use of the most recent Illumina MethylationEPIC Beadchip platform to characterize genome-wide DNA methylation changes observed through the first 10 years of life in longitudinal blood samples of 11 subjects. We described numerous changes during the first 5 years, while many less alterations in the following 5 year period. Interestingly, we identified a subset of persistent DNA methylation changes of considerable magnitude along the first 10 years of life. Moreover, our data demonstrated that genes that suffer simultaneous hyper- and hypomethylation are functionally different from genes that are exclusively hyper- or hypomethylated. Furthermore, our results evidence that enhancer-associated methylation changes are different for the gain or loss of methylation. throughout hematopoietic maturation by analyzing multiple hematopoietic cell types at different developmental stages. We identified a plethora of DNA methylation changes that occur during human hematopoietic differentiation. Interestingly, we observed that T lymphocytes display a substantial enhancement of de novo CpG hypermethylation as compared to other hematopoietic cell populations.
2019-01-07 | E-MTAB-7069 | biostudies-arrayexpress
Project description:Background Impaired interferon response and allergic sensitisation may contribute to virus induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDC) play a key role in antiviral immunity as critical producers of type I interferons (IFN-I). pDC also express the high affinity IgE receptor (FcRI) through which IFN-I production may be negatively regulated. If antiviral function of pDC is associated with recurrent episodes of wheeze in young children is not well understood. This study aimed to evaluate the phenotype and function of circulating pDC in children with a longitudinally defined wheezing phenotype. Methods We performed multiparameter flow cytometry on peripheral blood mononuclear cells from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDC from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database. Results We observed a significant depletion of circulating pDC in young children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the IgE receptor (FcRI) on their pDC. Based on transcriptomic analysis, pDC from these individuals did not mount a robust systemic antiviral response as observed in children who displayed a non-recurrent wheezing phenotype. Conclusion Our data suggests that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of FcRI is increased and their function as major IFN producers is impaired during acute exacerbations of wheeze.
2023-12-17 | GSE243052 | GEO
Project description:Whole blood transcriptomes from a longitudinal study of 5 Malawian children who first present with severe Plasmodium falciparum malaria, and return in one month with mild malaria We used microarrays to identify transcripts that were associated with each clinical presentation.
2012-01-11 | GSE33811 | GEO
Project description:Whole blood transcriptomes from a longitudinal study of 5 Malawian children who first present with severe Plasmodium falciparum malaria, and return in one month with mild malaria We used microarrays to identify transcripts that were associated with each clinical presentation. A blood sample was taken upon presentation during the severe and mild malaria episodes in 5 Malawian children (total n=5 pairs) followed by RNA extraction and hybridization on Affymetrix GeneChip Human Gene 1.0 ST Array, using a paired analysis
2012-01-11 | E-GEOD-33811 | biostudies-arrayexpress
Project description:The prevalence of atopic diseases has increased with atopic dermatitis (AD) as the earliest manifestation. We assessed if molecular risk factors in atopic mothers influence their offsprings’ susceptibility to an atopic disease. Pairs of pregnant women and their infants with or without parental atopy were followed over the first 2 years of life. Global DNA methylation and differentially methylated regions (DMR) were determined in atopic and non-atopic mothers. During the first 2 years of life, AD was more prevalent in children of atopic compared to non-atopic mothers with an increase in food sensitization in children with AD. 165 DMRs distinguished atopic from non-atopic mothers. Maternal atopy combined with DMRs increased the offsprings’ predicted risk to develop AD from an odds ratio of 2.56 to 4.26.
2022-12-15 | GSE163250 | GEO