Terman D S, Garcia-Rinaldi R, Dannemann B, Moore D, Crumb C, Tavel A, Poser R
Clin Exp Immunol. 1978 Oct;34(1):32-41.
The specific removal of circulating bovine serum albumin (BSA) antibodies in canine hosts with a BSA collodion charcoal extracorporeal immunoadsorbent is followed by a rebound and overshoot of specific antibody levels within 7 days after perfusion. Studies were carried out in dogs actively immunized to BSA and human serum albumin (HSA) to determine whether the post-immunoadsorption antibody rebound could be modified by the administration of various chemotherapeutic agents given alone or in combination, at various intervals in the post-perfusion period. Control extracorporeal immunoadsorption was carried out in each dog and its own pattern of post-perfusion antibody rebound was recorded. After a second extracorporeal perfusion, single drug chemotherapy with cyclophosphamide, methotrexate or cytosine arabinoside resulted in a slight delay, or had no effect on the recovery of antibody levels to pre-perfusion values. In contrast, dual (cyclophosphamide and cytosine arabinoside) or triple (cyclophosphamide, cytosine arabinoside and methotrexate) chemotherapy resulted in specific attenuation or arrest of BSA antibody rebound after specific immunoadsorption. BSA binding of serum rebounded to 62% of pre-perfusion values in one dog, but declined 37% and 22% below post-perfusion levels in two others. The immunosuppressive effect of dual or triple chemotherapy on BSA binding was specific, since control levels of HSA binding in sera were unchanged by the extracorporeal immunoadsorption and the chemotherapeutic treatment. Drug toxicity, including myelosuppression, diarrhoea and fever was transient and reversible upon cessation of treatment, but was more severe in dogs given a dual or triple drug treatment. Therefore, chemotherapeutic agents employed after extracorporeal immunoadsorption may result in specific reduction and lasting suppression of circulating antibody levels. Conclusions based on the number of dogs studied must be guarded, but these findings suggest a potentially effective therapeutic approach to many antibody mediated diseases.
用牛血清白蛋白火棉胶炭体外免疫吸附剂特异性去除犬宿主循环中的牛血清白蛋白（BSA）抗体后，灌注后7天内特异性抗体水平会出现反弹和超调。对主动免疫BSA和人血清白蛋白（HSA）的犬进行了研究，以确定免疫吸附后抗体的反弹是否可以通过在灌注后不同时间单独或联合给予各种化疗药物来改变。对每只犬进行对照体外免疫吸附，并记录其自身灌注后抗体反弹的模式。在第二次体外灌注后，用环磷酰胺、甲氨蝶呤或阿糖胞苷进行单一药物化疗会导致抗体水平恢复到灌注前值的时间稍有延迟，或无影响。相比之下，双重（环磷酰胺和阿糖胞苷）或三重（环磷酰胺、阿糖胞苷和甲氨蝶呤）化疗会导致特异性免疫吸附后BSA抗体反弹的特异性减弱或停止。一只犬血清中BSA结合反弹至灌注前值的62%，但另外两只犬的血清中BSA结合水平比灌注后水平分别下降了37%和22%。双重或三重化疗对BSA结合的免疫抑制作用是特异性的，因为体外免疫吸附和化疗处理后血清中HSA结合的对照水平未发生变化。包括骨髓抑制、腹泻和发热在内的药物毒性是暂时的，停药后可逆，但在接受双重或三重药物治疗的犬中更严重。因此，体外免疫吸附后使用化疗药物可能会导致循环抗体水平的特异性降低和持久抑制。基于所研究犬的数量得出的结论必须谨慎，但这些发现提示了一种对许多抗体介导疾病可能有效的治疗方法。
