Inflammatory signatures during the steady state of sickle cell disease in African children

Inflammation is a hallmark of sickle cell disease (SCD) and markers of inflammation could be used for disease stratification and subsequent therapeutic manipulation towards desirable clinical outcomes in children with SCD. The levels of 23 cytokines and full blood count (FBC) biomarkers were assayed using the Luminex technology and a five-part differential FBC among 63 children with SCD and 66 non-SCD controls. We also assessed the use of disease modifying agents like hydroxyurea, vitamins, and other drugs. All the cytokines except CCL2 and IL-1β were significantly higher among participants with SCD. However, IL-23p40 and IL-12p70 were significantly lower in the SCD group. Ratios of 1L-12p70, IL-23p40, and IL-1β (pro-inflammatory) against IL-4 and IL-10 (anti-inflammatory) were significantly lower while IL-1α, IL-17A, IL-3 ratios against IL-4 and IL-10 were higher in the SCD group. Also, the IL-4/10 ratio was significantly higher in the SCD cohort. Linear and quadratic discriminant analyses reported AUC of 0.998 and 1.000 and precision values of 0.94 and 1.00, respectively suggesting the biomarker profiles were distinct between the SCD and non-SCD cohorts. The steady state of SCD was characterized by an imbalanced cytokine milieu with the dominance of pro-inflammatory actors. Also IL-1α, IL-17A, IL-3, CCL3, and GM-CSF appeared to be the key drivers of subclinical inflammation in steady state whereas low levels of IL-12p70, IL-23p40, and IL-1β as well as high levels of IL-4 contributed to maintaining the steady state. Monitoring and manipulating these cytokines could thus help sustain and improve the steady-state in patients.