HO-1 levels/activity in innate immune cells of SCD patients in response to ongoing hemolysis is a critical switch between proinflammatory vs immunoregulatory states, which in turn affect alloimmunization risk. We hypothesize that SCD patients with high HO-1 levels/activity will effectively inhibit the proinflammatory cytokine IL-12 in response to extracellular cell free heme. This will result in higher Treg/T effector ratios, which in turn will suppress B-cell responses in these individuals, lowering their risk of alloimmunization. In contrast, low HO-1 levels/activity will lead to inability to dampen IL-12, thereby lowering Treg/T effector ratios and increasing the risk of alloimmunization.