Specificity of ubiquitin-positive inclusions in amyotrophic lateral sclerosis

泛素阳性的丝状包涵体被认为是肌萎缩侧索硬化症(ALS)特有的异常。然而，在其他神经疾病和非神经对照中，这种包涵体还没有得到充分的研究。为了评价细丝状包涵体的特异性，我们对23例ALS患者、31例19种不同神经系统疾病(非ALS)患者和37例正常对照的腰骶髓运动神经元进行了免疫组织化学和免疫电子显微镜观察。用抗泛素多克隆抗体对脊髓石蜡包埋切片进行免疫组化染色，并对脊髓前角运动神经元进行检测。在ALS中，我们发现了3种包裹体，即丝状包裹体和颗粒状包裹体，以及与路易体相对应的致密圆体。在23例ALS患者中有19例观察到丝状包涵体，在31例非ALS患者中有1例观察到丝状包涵体，但在37例对照组中均未发现丝状包涵体。肌萎缩侧索硬化症患者的丝状包涵体比非肌萎缩侧索硬化症患者或对照组更常见(p&lt；0.01)。非肌萎缩侧索硬化症患者有丝状包涵体，B细胞淋巴瘤浸润性周围神经近端，导致前角运动神经元明显的中枢色质溶解。免疫电子显微镜下，ALS的颗粒包涵体不仅含有与ALS的丝状包涵体相似的成分，还含有脂褐素颗粒，而淋巴瘤患者的丝状包涵体则表现为核糖体受累。虽然我们关于丝状夹杂物频率的数据进一步表明ALS中夹杂物的特异性，但在非ALS患者中也可能观察到类似的夹杂物，如果不相同的话。这表明泛素阳性的丝状包涵体是ALS的特征，但不是ALS的病因。

Ubiquitin-positive filamentous inclusions have been considered to represent abnormalities specific to amyotrophic lateral sclerosis (ALS). However, the inclusions have not yet been fully investigated in other neurological diseases and non-neurological controls. To evaluate the specificity of the filamentous inclusions, we studied, both immunohistochemically and immunoelectron microscopically, the motor neurons of the lumbosacral cords from 23 patients with ALS,31 patients with 19 different kinds of other neurological diseases (non-ALS) and 37 controls. We stained paraffin-embedded sections of the spinal cords by the avidin-biotin complex method using polyclonal anti-ubiquitin anti-bodies, and examined the anterior horn motor neurons. In ALS,we found 3 kinds of inclusions, i.e.filamentous and granular inclusions, and dense round bodies corresponding to Lewy bodies. Filamentous inclusions were observed in 19 of 23 patients with ALS,and in 1 of 31 non-ALS patients, but were not found in any of the 37 controls. Filamentous inclusions were more frequently observed in ALS patients than in non-ALS patients or controls (p<0.01). The non-ALS patient with filamentous inclusions had a B cell lymphoma which infiltrated the proximal parts of the peripheral nerves, causing marked central chromatolysis in the anterior horn motor neurons. On immunoelectron microscopy, the granular inclusions in ALS contained not only the constituents similar to those of the filamentous inclusions in ALS,but also lipofuscin granules, whereas the filamentous inclusions in the lymphoma patient showed the involvement of ribosomes. Although our data regarding the frequency of the filamentous inclusions further indicate the specificity of the inclusions in ALS,similar, if not identical, inclusions may also be observed in non-ALS patients. This suggests that ubiquitin-positive filamentous inclusions are characteristic of, but not pathognomonic of ALS.