Specificity of ubiquitin-positive inclusions in amyotrophic lateral sclerosis

泛素阳性丝状包涵体被认为是肌萎缩性侧索硬化症（ALS）特有的异常。然而，在其他神经系统疾病和非神经控制中尚未充分研究包涵体。为了评价丝状包涵体的特异性，我们采用免疫组织化学和免疫电镜对23例ALS患者、31例其他19种神经系统疾病（非ALS）患者和37例对照组的腰骶索运动神经元进行了研究。采用多克隆抗泛素抗体对脊髓石蜡包埋切片进行亲和生物素复合物染色，并检测脊髓前角运动神经元。在ALS中，我们发现了3种包裹体，即丝状和粒状包裹体，以及与路易体对应的致密圆形包裹体。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例对照中均未发现。肌萎缩侧索硬化症患者丝状包涵体的发生率高于非肌萎缩侧索硬化症患者和对照组（p<0.01）。非als患者伴丝状包涵体的B细胞淋巴瘤浸润周围神经近端，引起前角运动神经元明显的中央色素化。在免疫电镜下，ALS的颗粒状包涵体不仅含有与ALS的丝状包涵体相似的成分，而且含有脂褐质颗粒，而淋巴瘤患者的丝状包涵体则含有核糖体。虽然我们关于丝状包涵体频率的数据进一步表明了ALS包涵体的特异性，但在非ALS患者中也可能观察到类似的（如果不是完全相同的话）包涵体。这表明泛素阳性丝状包涵体是ALS的特征，但不是ALS的病理特征。

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.