Hinman C L, Stevens-Truss R
Department of Medicinal & Biological Chemistry, University of Toledo, Ohio 43606, USA.
Immunopharmacol Immunotoxicol. 1998 May;20(2):233-49. doi: 10.3109/08923979809038542.
Myasthenia gravis is an autoimmune disease in which antibodies are produced against one's acetylcholine receptors, resulting in complement-mediated membrane destruction and internalization of antibody-receptor complexes. Symptoms range from weakening of extraocular muscles to severe impairment of movement and breathing. Prior to administering a therapeutic agent to eliminate antibody-producing lymphocytes, it will be necessary to remove specific antibody from the circulation. This process was investigated in an animal model of ex vivo specific immunoadsorption using awake, conscious rabbits. Following arterial blood separation, plasma was pumped upward through an affinity column containing covalently-bound acetylcholine receptor. Treated plasma was returned to the rabbit. Within a one-hour ex vivo procedure, specific antibody levels could be lowered from 16.2 ng/ml to less than 0.6 ng/ml, a reduction of more than 95%. By washing the column, at least four exchanges could be performed before specific antibody removal significantly diminished. The effects of specific antibody removal upon muscle function varied among individual rabbits, but if symptoms were not severe following passive transfer of purified monoclonal antibody to induce myasthenia, removal of 60% of the total specific antibody resulted in clinical improvement, as monitored by an animal's response to gallamine triethiodide.
重症肌无力是一种自身免疫性疾病，在该疾病中会产生针对自身乙酰胆碱受体的抗体，导致补体介导的膜破坏以及抗体 - 受体复合物的内化。症状范围从眼外肌无力到严重的运动和呼吸功能损害。在施用治疗剂以消除产生抗体的淋巴细胞之前，有必要从循环中去除特异性抗体。在使用清醒、有意识的兔子的离体特异性免疫吸附动物模型中对该过程进行了研究。分离动脉血后，血浆向上泵入含有共价结合的乙酰胆碱受体的亲和柱。处理后的血浆返回兔子体内。在一小时的离体过程中，特异性抗体水平可从16.2 ng/ml降至低于0.6 ng/ml，降低幅度超过95%。通过洗涤柱子，在特异性抗体去除显著减少之前可进行至少四次交换。特异性抗体去除对肌肉功能的影响在个体兔子之间有所不同，但如果在被动转移纯化的单克隆抗体以诱导重症肌无力后症状不严重，去除60%的总特异性抗体可导致临床改善，这通过动物对三碘季铵酚的反应来监测。
