Drachman D B, Chaudhry V, Cornblath D, Kuncl R W, Pestronk A, Clawson L, Mellits E D, Quaskey S, Quinn T, Calkins A
Johns Hopkins University, School of Medicine, Baltimore, MD 21287-7519.
Ann Neurol. 1994 Feb;35(2):142-50. doi: 10.1002/ana.410350205.
Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double-blind, randomized, placebo-controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI-treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI-treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2-year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.
尽管肌萎缩侧索硬化症（ALS）的病因仍不明确，但近期研究提示其发病机制存在自身免疫机制。既往免疫抑制治疗试验结果尚无定论。我们的研究旨在确定全淋巴照射（TLI）产生的更强效、更持久的免疫抑制是否会改变ALS的病程。在一项双盲、随机、安慰剂对照研究中，30例典型ALS患者接受TLI治疗，31例接受假照射。对肌肉力量、功能性运动活动以及体液和细胞免疫状态进行定量测量，随访2年，或直至死亡或依赖呼吸机。在整个研究过程中，TLI治疗组和对照组的运动功能无显著差异。TLI治疗组和对照组的总体生存率无显著差异。在整个2年研究期间，TLI有效抑制了细胞和体液免疫功能。对免疫抑制与运动功能之间关系的分析显示，治疗效果不一致。我们得出结论，TLI产生的强效、持久免疫抑制对ALS患者无益处。这并不支持ALS发病机制的自身免疫机制这一概念。
