title: Complement inhibitors to treat IgM-mediated autoimmune hemolysis.
abstract: Complement activation in autoimmune hemolytic anemia may exacerbate extravascular hemolysis and may occasionally result in intravascular hemolysis. IgM autoantibodies as characteristically found in cold autoantibody autoimmune hemolytic anemia, in cold agglutinin disease but also in a considerable percentage of patients with warm autoantibodies are very likely to activate complement in vivo. Therapy of IgM-mediated autoimmune hemolytic anemia mainly aims to decrease autoantibody production. However, most of these treatments require time to become effective and will not stop immediate ongoing complement-mediated hemolysis nor prevent hemolysis of transfused red blood cells. Therefore pharmacological inhibition of the complement system might be a suitable approach to halt or at least attenuate ongoing hemolysis and improve the recovery of red blood cell transfusion in autoimmune hemolytic anemia. In recent years, several complement inhibitors have become available in the clinic, some of them with proven efficacy in autoimmune hemolytic anemia. In the present review, we give a short introduction on the pathogenesis of autoimmune hemolytic anemia, followed by an overview on the complement system with a special focus on its regulation. Finally, we will discuss complement inhibitors with regard to their potential efficacy to halt or attenuate hemolysis in complement-mediated autoimmune hemolytic anemia.
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, the Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, the Netherlands Department of Hematology, Academic Medical Center, University of Amsterdam, the Netherlands s.s.zeerleder@amc.uva.nl.
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects*; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology
chemical_list: D001323:Autoantibodies; D051056:Complement Inactivating Agents; D007075:Immunoglobulin M; D003165:Complement System Proteins