Murine Model of Autoimmune Hemolytic Anemia: Red Blood Cell Clearance Mechanisms and Treatment Efficacy

Antibodies against erythrocyte-specific antigens can cause immune red blood cell (RBC) destruction, resulting in autoimmune hemolytic anemia (AHA). Therapy for patients with AHA remains a challenge, and better knowledge of pathophysiological mechanisms is needed. In this thesis, the mechanisms of RBC clearance mediated by a panel of monoclonal anti-mouse RBC antibodies were characterized in a murine model of passive AHA, and efficacy of treatments was evaluated. It is demonstrated herein that mechanisms in addition to the classical macrophage Fcγ receptor (FcγR)- and/or complement-mediated hemolysis may be contributing to the development and/or persistence of anemia. The efficacy of intravenous immunoglobulin (IVIg) therapy varies in relation to the mechanism of anemia in mice with FcγR-mediated anemia being highly related to IVIg responsiveness. In addition, this thesis shows that monoclonal RBC-specific antibodies can ameliorate thrombocytopenia in a murine model of passive immune thrombocytopenia (ITP) analogous to the use of anti-D in ITP patients.MAS