Alterations in the humoral immunophenotype in sickle cell disease.

The pathophysiology of sickle cell disease (SCD) is linked to haemolysis and systemic inflammation. To determine the range of systemic alterations, we assessed the frequency of 12 immune populations and the levels of related cytokines in the peripheral blood of paediatric (n = 13) and adult (n = 12) patients with SCD prescribed hydroxyurea, as compared to paediatric (n = 5) and adult (n = 10) race-matched controls. Transcriptome analysis of the peripheral blood of paediatric SCD patients and controls was also performed. Flow cytometry showed a 3.5-fold increase (p = 0.005) in CD19+ B cells in paediatric SCD and a 52% decrease in central memory B cells (p = 0.002) in adult SCD. Paediatric transcriptomic data revealed significant upregulation of pro-B cell transcripts (27 genes, top 3: E2F2, RAD51, ASPM) and plasma cell transcripts (37 genes, top 3: IGF1, TNFRSF17, DERL3). Cytokine analyses showed significant increases in IL-2 (p = 0.013), IL-4 (p = 0.026), TNFβ (p = 0.039), IL-13 (p = 0.034) and BAFF (p = 0.041) in paediatric SCD, and an increase in CD40L and BAFF in adult SCD. In summary, our data showed alterations in the humoral immophenotype in paediatric SCD, specifically an increase in CD19+ B cells, suggesting there may be significant alterations of homeostasis in the humoral immune system in children with SCD treated with hydroxyurea.