Pestronk A, Drachman D B, Adams R N
Muscle Nerve. 1982 Jan;5(1):79-84. doi: 10.1002/mus.880050115.
We have treated animals with an ongoing autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), using a strategy designed to eliminate the antibody-producing cells. During well-established EAMG, a single high dose of cyclophosphamide was given because of its known effectiveness against B-lymphocytes. To counteract the lethal effects of the drug, the rats were "rescued" by bone marrow cell transplantation. This treatment produced a rapid and sustained fall of antibody titers against both the immunizing antigen (Torpedo acetylcholine receptor) and the autoantigen (rat acetylcholine receptor). Immunologic memory, as measured by an anamnestic response to the antigen, was partially suppressed. Cyclophosphamide treatment produced improvement in the neuromuscular defect: treated animals had, on the average, twice as many acetylcholine receptors at neuromuscular junctions compared with untreated EAMG animals. This treatment method of short-term high doses of an immunosuppressive drug, such as cyclophosphamide, may eventually prove useful for human myasthenia gravis and other autoimmune diseases.
我们采用一种旨在消除产生抗体细胞的策略，对患有进行性自身免疫性疾病——实验性自身免疫性重症肌无力（EAMG）的动物进行了治疗。在已确诊的EAMG期间，给予单次高剂量环磷酰胺，因为已知其对B淋巴细胞有效。为抵消该药物的致死作用，通过骨髓细胞移植对大鼠进行“挽救”。这种治疗使针对免疫抗原（鱼雷乙酰胆碱受体）和自身抗原（大鼠乙酰胆碱受体）的抗体滴度迅速且持续下降。通过对抗原的回忆反应测定的免疫记忆被部分抑制。环磷酰胺治疗使神经肌肉缺陷得到改善：与未治疗的EAMG动物相比，接受治疗的动物神经肌肉接头处的乙酰胆碱受体平均数量多两倍。这种短期高剂量免疫抑制药物（如环磷酰胺）的治疗方法最终可能被证明对人类重症肌无力和其他自身免疫性疾病有用。
