MicroRNA 221 Expression by Leukocytes Correlates with the Clinical Severity of Sickle Cell Disease

Objective: The severity of sickle cell disease (SCD) increases with neutrophil count and expression of adhesion molecules by leukocytes. Intercellular adhesion molecule one (ICAM-1) on vascular endothelium mediates leukocyte adherence to the blood vessel wall. This contributes to vaso-occlusion and tissue damage in SCD. Micro-RNA 221 (MIR 221) regulates the gene for ICAM-1. The purpose of this study was to evaluate the relationship between the severity of SCD and expression of MIR 221 by leukocytes. Methods: SCA severity scores were determined in 73 HbSS patients during steady state; and leukocyte expression of MIR 221, complete blood count and plasma level of soluble ICAM-1 (sICAM-1) measured during vaso-occlusive crisis and steady state. Sample estimates inferred to target population with a p value set at 0.05. SCA severity score was correlated to laboratory parameters. Results: Median values of MIR221 increased from mild (3092 copies/ng of cDNA) through moderate (4004 copies/ng) to severe SCA (median 5587 copies/ng, p< 0.05). Spearman's correlation coefficient (Rho) between severity scores in severe SCA and steady state MIR 221 was high at 0.9. Conclusion: Leukocyte MIR 221 is a strong correlate of SCA severity, and a candidate biomarker for assessing the disease severity in the clinical setting.