Cytokine and chemokine signatures of steady-state sickle cell disease in African children: a cross-sectional study.

BACKGROUND

Sickle cell disease (SCD) is characterized by chronic inflammation, yet the inflammatory landscape defining the clinically defined steady state remains poorly characterized, particularly in African populations where the disease burden is highest. Understanding baseline cytokine and chemokine signatures during the steady state is important for distinguishing physiological disease equilibrium from transitions toward acute complications.

METHODS

We conducted a cross-sectional study of 129 children aged 2-17 years in Ghana, including 63 children with SCD in steady state and 66 healthy controls. Serum concentrations of 23 cytokines and chemokines were quantified using multiplex immunoassays alongside full blood count parameters. Comparative analyses and cytokine ratio assessments were performed to characterize steady-state SCD inflammatory signatures.

RESULTS

Most pro-inflammatory cytokines and chemokines were significantly elevated in children with SCD compared with controls. However, IL-12p70 and IL-23p40 levels were significantly reduced in the SCD cohort, while CCL2 and IL-1β showed no significant differences between groups. Ratio analyses revealed lower IL-12p70/IL-4, IL-23p40/IL-4, and IL-1β/IL-10 ratios, alongside increased IL-1α/IL-4, IL-17A/IL-10, IL-3/IL-10, CCL3/IL-10, and GM-CSF/IL-10 ratios, indicating an imbalanced inflammatory milieu dominated by pro-inflammatory signals. Discriminant analyses using cytokine and hematological parameters further demonstrated clear separation between children with SCD and controls.

CONCLUSIONS

Steady-state SCD in African children is characterized by a distinct cytokine and chemokine profile marked by persistent pro-inflammatory activation alongside regulatory counterbalances. Reduced ratios of IL-12p70 and IL-23p40 relative to anti-inflammatory cytokines may contribute to maintaining the steady-state inflammatory equilibrium. These findings provide reference signatures that may support future studies investigating inflammatory biomarkers.