Prolongation of sickle cell survival by dimethyl adipimidate is compromised
by immune sensitization
MS Guis, WM Lande, N Mohandas, R Pennathur-Das, H Preisler, BH Lubin and WC Mentzer
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.
Volume 64,
Issue 1,
pp. 161-165,
07/01/1984
Copyright © 1984 by The American Society of Hematology