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Whole-blood transcriptome profile in children with sickle cell anemia before and after exercise

ABSTRACT: Patients with sickle cell anemia (SCA) show higher levels of circulating pro-inflammatory cytokines and endothelial activation markers compared to healthy peers and altered blood transcriptome profiles. However, the characterization of the whole-blood transcriptome profile in response to exercise has not been evaluated in children with SCA. Twenty-three children/adolescents with SCA (10-19 years old) and 17 healthy controls (10-22 years old) performed eight 2-min bouts of cycle ergometry interspersed with 1-min rest intervals (50% or 70% of the peak workload achieved during the cardiopulmonary exercise test). Whole-blood transcriptome profile (RNA-seq) was performed before and after the exercise protocol. Following exercise, gene pathways associated with innate immunity were altered in both children with SCA and controls. Our results shed light on the common and different immune responses to acute exercise at the molecular level in children with SCA and healthy controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244401 | GEO | 2024/05/24

REPOSITORIES: GEO

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Project description:Background: The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in the pediatric population. We set out to investigate the effect of a 20-week exercise intervention on whole blood transcriptome profile (RNA-seq) in children with overweight/obesity. Methods: Twenty-four pre-pubertal children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n=10), or to a non-exercise control group (usual lifestyle, n=14). Whole blood transcriptome profile was analysed using RNA-seq STRT2 technique. Gene expression analysis was carried out with the Limma R/Bioconductor software package, and the gene ontology (GO) and pathway enrichment analyses were performed using R. Ingenuity Pathway Analysis (IPA) was performed for gene network detection. The transcriptome data were in silico validated using PHENOPEDIA and meta-analysis database extrameta.org. Results: 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value < 0.05), while after multiple correction, no significant difference between groups persisted in gene expression profiles (FDR > 0.05). Based on non-corrected analyses, the enriched GO processes and molecular pathways highlighted the effect of exercise on different immune response related pathways in boys (antigen processing and presentation, infections, and T cell receptor complex) and girls (Fc epsilon RI signaling pathway) (FDR < 0.05). In silico data mining and validation analyses (using PHENOPEDIA and meta-analysis database extrameta.org) highlight top genes regulated by exercise such as CD6, HLA-C, TNFRSF1A, MYD88, and NFKBIA genes in boys and RAC1, ANXA6, FYN, INPP5D, PIK3CD and SPARC genes in girls. Conclusion: These results suggest that 20-week exercise program influences different immune processes in children with overweight/obesity. The transcriptome differences between boys and girls could partly be explained, in addition to the gender differences, by the distinct intensity in the exercise intervention as boys had stronger exercise stimulus in training. Our findings should be considered exploratory and preliminary given the relatively small sample size. Larger and more powered randomized controlled trials should confirm or contrast our findings.

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Whole-blood transcriptome profile in children with sickle cell anemia before and after exercise

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