Oxidantscan: A novel biomarker to assess red blood cell susceptibility to oxidative stress in sickle cell disease

Abstract

Red blood cells (RBC) from patients with sickle cell disease (SCD) are continuously exposed to high levels of oxidative stress, which impacts RBC deformability. In this study, we applied a novel technique (oxidantscan) to measure deformability of RBCs under shear stress while exposed to oxidative stress. Using RBCs collected from a cohort of patients with SCD and healthy volunteers, we measured different parameters including T-POD (Time to initiate Oxidant-induced change in Deformability) and EIMin (the minimum deformability reached during the test). T-POD was significantly shorter in patients with HbSS ( n = 21, 729 ± 410 s) and HbSC ( n = 19, 1031 ± 225 s) when compared to healthy controls ( n = 20, 1739 ± 328 s, p < 0.05). Also EIMin was significantly lower in patients with HbSS (0.26 ± 0.10) and HbSC (0.30 ± 0.10) compared to healthy controls (0.54 ± 0.02). These results indicate that RBCs from patients with SCD are more susceptible to oxidative stress, which can be measured in a reproducible and quantifiable way. We also demonstrate that Oxidantscan outcome parameters correlated with sickling behavior and markers of hemolysis, indicating a possible link between these key pathophysiological features and the ability to withstand oxidative stress (all p < 0.05). Finally, we provide preliminary evidence for the potential of this technique to evaluate antioxidant therapy with l -glutamine as SCD RBCs showed a significant improvement in T-POD (11.5 %, p = 0.01) and EIMin (46.9 %, p = 0.03) upon ex vivo treatment with l -glutamine. The Oxidantscan is a promising technique for evaluating the response of SCD RBCs to oxidative stress, providing new insights in disease pathophysiology and potential novel treatment strategies.