Whole-blood transcriptome analysis reveals distinct gene expression signatures in paediatric patients with sickle cell anaemia before and after exercise

Br J Haematol. 2024 Jul;205(1):320-328. doi: 10.1111/bjh.19533. Epub 2024 May 20.

Abstract

Sickle cell anaemia (SCA) patients display elevated levels of circulating pro-inflammatory cytokines and endothelial activation markers compared to healthy peers. The impact of exercise on the pro-inflammatory state in SCA remains unclear. This study aimed to characterize the whole-blood transcriptome profile in response to an acute bout of exercise in paediatric SCA patients. Twenty-three SCA participants (13 ± 3 years, 52% girls) and 17 healthy controls (14 ± 3 years, 29% girls) performed eight 2-min bouts of cycle ergometry interspersed with 1-min rest intervals. Whole-blood transcriptome profile (RNA-seq) was performed before and after exercise. At baseline, gene pathways associated with gas transport in erythrocytes were up-regulated in SCA patients compared to controls. Following exercise, gene pathways associated with innate immunity were altered in both groups. Interaction analyses revealed 160 annotated genes (101 up- and 59 down-regulated) that differentially altered by exercise in SCA patients. Moreover, genes that exhibited a blunted response to exercise in SCA patients were enriched in the IL-17 signalling pathway, suggesting an impaired innate immune response to exercise. This data will contribute to the development of evidence-based exercise prescription guidelines for this patient population.

Keywords: fitness; immune function; omics; physical activity.

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell* / blood
  • Anemia, Sickle Cell* / genetics
  • Anemia, Sickle Cell* / therapy
  • Case-Control Studies
  • Child
  • Exercise* / physiology
  • Female
  • Gene Expression Profiling*
  • Humans
  • Immunity, Innate
  • Male
  • Transcriptome*