Guis M S, Lande W M, Mohandas N, Pennathur-Das R, Preisler H, Lubin B H, Mentzer W C
Blood. 1984 Jul;64(1):161-5.
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.
在体外已证明具有抗镰状化特性的氨基反应性交联剂己二酸二甲酯(DMA),对5名成年男性镰状细胞贫血患者51Cr标记的自体镰状细胞存活的影响进行了评估。用5 mmol/L DMA(pH 7.4)预处理的细胞,4名受试者的细胞存活正常(半衰期28 - 33天),第5名受试者的细胞存活接近正常(半衰期20天),其存活时间比镰状细胞病中通常观察到的要长得多。事实上,DMA对体内镰状细胞存活的影响等于或超过了迄今为止测试的任何其他药物。在3名受试者中,第二次输注经DMA处理的红细胞的存活时间(半衰期1.8、3、4.5天)比初始研究中的要短得多。在这些受试者的血清中检测到一种针对经DMA处理的红细胞的抗体。在进一步考虑将DMA用于镰状细胞贫血治疗之前,需要改变处理后细胞的免疫原性。