What is complement-mediated cytotoxicity and in which clinical context is it most relevant?

• A. Antibody binding activates complement leading to target cell lysis; relevant in transfusion reactions and some autoimmune cytopenias
• B. T-cell mediated cytotoxicity
• C. Phagocytosis by macrophages
• D. Antibody-dependent enhancement

Answer: (A)

Complement-mediated cytotoxicity occurs when antibodies bound to target cells activate the classical complement pathway, triggering the assembly of the membrane attack complex that creates pores in the cell membrane and causes rapid lysis of the target cell. Clinically, this is most relevant in transfusion reactions where donor red blood cells are targeted by patient antibodies that fix complement, and in some autoimmune cytopenias where autoantibodies activate complement to destroy circulating cells intravascularly. This mechanism is distinct from T-cell–mediated cytotoxicity, which uses cytotoxic T cells, and from phagocytosis by macrophages, which relies on opsonization to promote ingestion rather than direct lysis. Antibody-dependent enhancement is a different phenomenon related to viral infections and Fc receptor–mediated effects, not direct complement-mediated cytotoxicity.