Westarp M E, Fuchs D, Bartmann P, Hoff-Jörgensen R, Clausen J, Wachter H, Kornhuber H H
Department of Neurology, Ulm University, Germany.
Eur J Med. 1993 Jun-Jul;2(6):327-32.
The most frequent sporadic adult motor neuron disease, amyotrophic lateral sclerosis, affects more men, follows no epidemiologic pattern, and was long considered a pure spinal cord disorder. It now becomes evident that the disease is characterized by spinal, cerebral and extra-neuromuscular changes including B-cellular responses and ultrastructural skin alterations. Do these parameters identify subgroups or correlate with the male preponderance of the disease?
We analyzed age at and site of onset, sex, duration of clinical disease, and human foamy retroviral seroreactivity in 47 consecutive patients with a definite diagnosis of amyotrophic lateral sclerosis. The results were compared with antivisna seroreactivity, immunoglobulin isotypes, circulating immune complexes, neopterin and beta 2-microglobulin as well as skin biopsies in respective subsets of the same 47 patients.
Seroreactivity to recombinant human spuma retrovirus (HSRV) envelope and/or capsid protein was positive in 20/47 amyotrophic lateral sclerosis patients, and 28/30 competed with specific retroviral antibodies on maedi-visna antigen. Anti HSRV-seronegative patients had lower immunoglobulin IgG3 isotype concentrations, while HSRV-gag plus HSRV-env antibody positives demonstrated highest circulating IgG immune complexes. All 11 amyotrophic lateral sclerosis patients partially reacting to recombinant HSRV-env or HSRV-gag antigen were men, and male amyotrophic lateral sclerosis patients tended to have higher total cerebrospinal fluid protein levels. Neopterin and beta 2-microglobulin as markers of a cellular immune activation remained basically normal in serum and cerebrospinal fluid.
We suggest a particular B-lymphocytic and retroviral involvement in this enigmatic, relentlessly progressing, at present untreatable and most frequent neurological system degeneration. To our opinion this situation justifies the search for novel anti-retroviral therapeutic strategies.
最常见的散发性成人运动神经元疾病——肌萎缩侧索硬化症，男性患者更多，无流行病学规律，长期以来被认为是一种单纯的脊髓疾病。现在很明显，该疾病的特征是脊髓、大脑和神经外肌肉的变化，包括B细胞反应和超微结构皮肤改变。这些参数能否识别亚组或与该疾病的男性优势相关？
我们分析了47例确诊为肌萎缩侧索硬化症的连续患者的发病年龄、发病部位、性别、临床疾病持续时间以及人类泡沫逆转录病毒血清反应性。将结果与同一47例患者各亚组中的抗维斯纳病毒血清反应性、免疫球蛋白同种型、循环免疫复合物、新蝶呤和β2-微球蛋白以及皮肤活检结果进行比较。
47例肌萎缩侧索硬化症患者中有20例对重组人泡沫逆转录病毒（HSRV）包膜和/或衣壳蛋白的血清反应呈阳性，28/30例在梅迪-维斯纳抗原上与特异性逆转录病毒抗体发生竞争。抗HSRV血清阴性的患者免疫球蛋白IgG3同种型浓度较低，而HSRV-gag加HSRV-env抗体阳性者循环IgG免疫复合物水平最高。对重组HSRV-env或HSRV-gag抗原部分有反应的11例肌萎缩侧索硬化症患者均为男性，男性肌萎缩侧索硬化症患者的脑脊液总蛋白水平往往较高。血清和脑脊液中作为细胞免疫激活标志物的新蝶呤和β2-微球蛋白基本保持正常。
我们认为在这种神秘的、持续进展的、目前无法治疗且最常见的神经系统退行性疾病中存在特定的B淋巴细胞和逆转录病毒参与。我们认为这种情况有理由寻求新的抗逆转录病毒治疗策略。
