Experimental model of autoimmune hemolytic anemia induced in mice with levodopa.

This paper describes an experimental model of autoimmune hemolytic anemia induced with multiple injections of levodopa. The serum antibodies were detected by indirect enzyme-linked immunosorbent assay (ELISA) and autoantibodies bound to syngeneic erythrocytes were detected by direct ELISA. A strain of mice injected with levodopa, at doses which are approximately equivalent to those used in human therapy, developed early and late cycles of IgM and IgG anti-mouse red blood cell (MRBC) autoantibody responses. These responses were followed by binding of IgM and IgG autoantibodies to the syngeneic erythrocytes and by two phases of anemia. Different strains of mice exhibited different sensitivities to Levodopa treatment, suggesting that genetic factors affect the anti-MRBC autoantibody response to levodopa. Indirect ELISA revealed that mice subjected to both X-irradiation (250 rad) and levodopa treatment had higher levels of IgG anti-MRBC autoantibodies than mice subjected to levodopa treatment alone, suggesting that a radiosensitive suppressor mechanism controls the autoantibody response. The autoantibodies induced with levodopa exhibited an unrestricted specificity and retained significant activity after absorption of MRBC. Serum autoantibodies were also detected by indirect ELISA in the sera of normal mice. This "natural" autoimmunity was mouse strain dependent and was possibly further influenced by environmental factors. The various implications of this model of autoimmune hemolytic anemia are discussed.