Table 2.
Examples of questions amenable to study with mouse models of RBC clearance
| Mechanism |
| Why are subpopulations of incompatible RBCs resistant to IgG- and/or IgM-mediated RBC clearance? |
| What signaling pathways produce the cytokine storm induced by haemolytic transfusion reactions? |
| Why are some haemolytic transfusion reactions clinically severe, whereas others are benign? |
| What host and donor factors influence RBC alloimmunization to allogeneic transfusions? |
| Can a mouse model of HDN be constructed to study immunization, immunomodulation and pathogenesis? |
| RBC storage |
| Can new storage solutions be developed to minimize the RBC storage lesion? |
| What biomarkers identify RBCs that are more prone to clearance in vivo after refrigerated storage in vitro? |
| Why do RBCs from some donors not perform well in vivo after refrigerated storage in vitro? Is this genetically determined? |
| Autoimmunity |
| Why is Band 3 the dominant autoantigen in NZB mice with AIHA? |
| What is the mechanism(s) for initiating the production of RBC autoantibodies? |
| Antigen loss |
| Does antigen loss occur more commonly than is currently believed? |
| What is the mechanism(s) responsible for antigen loss? |
| What factors determine whether RBC antigens are specifically removed from the RBC surface or whether the intact RBC is ingested? What are the roles in antigen loss of the antigen, the antibody, the macrophage and combinations thereof? |
| Treatment |
| What therapies can reduce antibody-mediated clearance and ameliorate the downstream consequences of this clearance? |
| Is there evidence that any of the following approaches are beneficial: corticosteroids, intravenous immunoglobulin, other immunosuppressants and complement-inhibitors? |
AIHA, autoimmune haemolytic anaemia, HDN, haemolytic disease of the newborn, NZB, New Zealand Black.