Prolongation of sickle cell survival by dimethyl adipimidate is compromised by immune sensitization

Abstract

The effect of dimethyl adipimidate (DMA), an amino-reactive crosslinking reagent with demonstrated antisickling properties in vitro, on the survival of 51Cr-labeled autologous sickle cells was evaluated in five adult males with sickle cell anemia. The survival of cells pretreated with 5 mmol/L DMA (pH 7.4), normal (t1/2 28-33 days) in four subjects and near-normal (t1/2 20 days) in the fifth, was considerably longer than that usually observed in sickle cell disease. In fact, the effect of DMA on the survival of sickle cells in vivo equals or exceeds that of any other agent tested to date. In three subjects, the survival of a second infusion of DMA-treated red cells was much shorter (t1/2 1.8, 3, 4.5 days) than in the initial study. An antibody was detected in the serum of these subjects that was directed to DMA-treated red cells. Modification of the immunogenicity of treated cells will be required before further consideration of DMA for use in the therapy of sickle cell anemia.