Cytotoxic antibodies trigger inflammation through Fc receptors

AbstractPathogenic self-reactive antibodies are a significant cause of morbidity and mortality and contribute to both cytotoxic and Immune complex-triggered Inflammatory disorders, typified by rheumatic diseases, autoimmune hemolytic anemia, and thrombocytopenla. Roles have been proposed for Fc receptors, complement, and complement receptors in the pathogenesis of these disorders, although the contribution of each to autoimmune injury is unclear. γ chain-deficient mice lacking FcγRI and FcγRlll are resistant to the development of experimental Immune hemolytic anemia induced by polyclonal rabbit anti-mouse red blood cell IgG antibodies. This resistance Is primarily a consequence of ineffective erythrophagocytosis, resulting from the lack of FcyRs on mononuclear phagocytes. Similarly, γ chain-deficient mice are completely resistant to the development of experimental immune thrombocytopenia induced by mouse anti-platelet antibodies. These data suggest that Fc receptors play an integral role in the pathogenesis of type II hypersensitivity and suggest potential therapeutic benefits of Fc receptor blockade