Mechanisms underlying red‐cell alloimmunization in sickle‐cell disease

Red blood cell transfusion is a life-sustaining therapy that has decreased morbidity and mortality in sickle-cell disease (SCD). The major immunological risk of transfusion is erythrocyte alloimmunization, which can lead to severe complications, such as delayed haemolytic transfusion reactions (DHTR) and problems finding compatible units, delaying transfusion. In this review, we discuss the known mechanisms of alloimmunization in sickle-cell disease and the extent to which findings from mouse models of immunization can be extrapolated to the setting of transfusion in humans with SCD. We also consider preventive treatments, such as B-lymphocyte depletion therapy.