The interplay between the innate immune system and immune haemolytic anaemia

Abstract

Immune haemolytic anaemia (IHA) is characterized by an increased breakdown of red blood cells (RBCs) due to allo‐ or auto‐antibodies directed toRBCantigens with or without complement activation. Based on the nature of the antibodies,IHAcan be divided in three main categories: autoimmune, drug‐induced and alloimmune‐mediatedIHA. There is growing evidence that the innate immune system plays an important role in the pathogenesis ofIHA. Complement‐mediated haemolysis with the subsequent release of cell‐free haemoglobin and cell‐free haem resulting in the generation of reactive oxygen species and cytotoxicity as well as the production of anaphylatoxins induce a systemic inflammatory response, which contributes to morbidity and mortality inIHA. The natural plasma scavengers of cell‐free haemoglobin and cell‐free haem, haptoglobin and hemopexin, respectively, are depleted in cases of chronic or severeIHA. The inducible enzyme haem oxygenase 1 (HO‐1) is an efficient cellular scavenger degrading haem into anti‐inflammatory products to partially limit haem‐mediated oxidative damage in cases of saturated scavenging capacity. Complement‐targeted therapy and the therapeutic replenishment of haptoglobin and hemopexin as well as the induction ofHO‐1 expression might be suitable targets in the treatment ofIHA.