Terman D S, Stewart I, Robinette J, Carr R, Harbeck R
Clin Exp Immunol. 1976 May;24(2):231-7.
The selective removal of circulating antibody specific for DNA was affected with an immuno-absorbent consisting of DNA-cellulose incorporated into agar gel. Antisera to DNA obtained from patient with systemic lupus erythematosus was circulated in vitro through experimental and control columns by a dual channel haemodialysis pump and serial aliquots were withdrawn and assayed for antibody. A 65% reduction in DNA binding of serum was achieved at a flow rate of 210 ml/min over a 4-hr period with no release of 125I-labelled DNA from the column into the serum. For in vivo studies, 2-6-3-8 kg rabbits were actively immunized with methylated bovine serum albumin conjugated to single-stranded DNA (MBSA-ssDNA). Whole blood was pumped from the femoral artery through an immuno-adsorbent composed of ssDNA-cellulose in an agar matrix. Results showed significant reductions in ssDNA binding activity over various periods after connection of the rabbit's circulation to the immuno-adsorbent with only minimal changes in BSA binding during the same period. Little release of incorporated 125I-labelled DNA from the column as assayed in the blood and tissues of the experimental animals occurred during the procedure. The immuno-adsorbent columns showed no residual cellular debris or thrombotic material. These results suggest that this immuno-adsorbent system may be used to specifically withdraw circulating DNA antibodies in vivo. Such a system may have clinical potential for specific therapy of systemic lupus erythematosus.
采用由掺入琼脂凝胶的DNA-纤维素组成的免疫吸附剂,实现了对循环中DNA特异性抗体的选择性去除。通过双通道血液透析泵,将系统性红斑狼疮患者的抗DNA血清在体外循环通过实验柱和对照柱,并抽取系列等分试样检测抗体。在4小时内,以210毫升/分钟的流速,血清的DNA结合力降低了65%,且柱中的125I标记DNA未释放到血清中。对于体内研究,用与单链DNA偶联的甲基化牛血清白蛋白(MBSA-ssDNA)对2-6-3-8千克的兔子进行主动免疫。全血从股动脉泵出,通过琼脂基质中由ssDNA-纤维素组成的免疫吸附剂。结果显示,在将兔子的循环与免疫吸附剂连接后的不同时间段内,ssDNA结合活性显著降低,而同期BSA结合仅有微小变化。在该过程中,实验动物血液和组织中检测到的柱中掺入的125I标记DNA释放极少。免疫吸附柱未显示残留细胞碎片或血栓物质。这些结果表明,这种免疫吸附系统可用于在体内特异性去除循环中的DNA抗体。这样的系统可能对系统性红斑狼疮的特异性治疗具有临床潜力。