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

Abstract

SummarySickle 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.