Warm antibody autoimmune hemolytic anemias are mediated by which immunoglobulin?

• A. IgM
• B. IgA
• C. IgE
• D. IgG

Answer: (D)

Warm autoimmune hemolytic anemia is driven by IgG autoantibodies that bind red blood cells at body temperature. Once IgG coats the RBCs, these cells are primarily cleared by splenic macrophages through Fc gamma receptor–mediated phagocytosis, leading to extravascular hemolysis and often the presence of spherocytes on a blood smear. The direct Coombs test typically detects IgG on the cell surface. Although complement may be activated secondarily, the main process is Fc-mediated removal of antibody-coated RBCs by the spleen. In contrast, IgM mediates cold agglutinin disease with robust complement activation and intravascular hemolysis at cold temperatures, and IgA or IgE are not the usual mediators of this condition.