Ohguro H, Chiba S, Igarashi Y, Matsumoto H, Akino T, Palczewski K
Department of Ophthalmology, Sapporo Medical College, Japan.
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3241-5. doi: 10.1073/pnas.90.8.3241.
Multiple sclerosis (MS), one of the most common chronic neurologic diseases, is characterized by the presence of multiple plaques of demyelination throughout the central nervous system. Although the etiology of the disease has not been established, it is believed to involve autoimmune mechanisms. We have examined sera from patients with MS for the presence of antibodies to antigens from brain and retina. Immunoblot analysis of soluble fraction of proteins from bovine brain revealed a prominent band at 45 kDa stained with sera of 8-14 patients with MS. In two patients with MS, serum antibody titers during relapse were higher compared with those when the patients were in remission. These antibodies were undetectable in cerebrospinal fluid of our MS patients and additionally were absent in sera of patients with other neurological diseases and normal control subjects. Furthermore, immunoblot analysis of the soluble fraction from bovine retinal rod outer segments revealed a prominent protein band at 48 kDa stained with MS sera. This antigen was purified to homogeneity from bovine retinal outer segments and identified as arrestin. Additionally, sera from MS patients reacted with purified beta-arrestin 1, a 45-kDa protein homologous to arrestin that is found in various tissues. Using limited proteolysis of arrestin and a competitive ELISA test with a synthetic peptide, we identified the recognition site(s) for antibodies in sera of MS patients at a dominant immunogenic site on arrestin located at the C-terminal region of the molecule. We suggest that the presence of circulating antibodies reactive with beta-arrestin or arrestin may be related to the course of MS progression.
多发性硬化症（MS）是最常见的慢性神经疾病之一，其特征是在整个中枢神经系统中存在多个脱髓鞘斑块。尽管该疾病的病因尚未明确，但据信涉及自身免疫机制。我们检测了MS患者血清中针对脑和视网膜抗原的抗体。对牛脑蛋白质可溶性部分的免疫印迹分析显示，在45 kDa处有一条明显的条带，可被8至14例MS患者的血清染色。在两名MS患者中，复发期间的血清抗体滴度高于缓解期。在我们的MS患者脑脊液中未检测到这些抗体，此外，其他神经疾病患者和正常对照受试者的血清中也没有这些抗体。此外，对牛视网膜视杆细胞外段可溶性部分的免疫印迹分析显示，在48 kDa处有一条明显的蛋白质条带，可被MS血清染色。该抗原从牛视网膜外段纯化至同质，并被鉴定为抑制蛋白。此外，MS患者的血清与纯化的β-抑制蛋白1发生反应，β-抑制蛋白1是一种与抑制蛋白同源的45 kDa蛋白质，存在于各种组织中。通过对抑制蛋白进行有限的蛋白水解以及使用合成肽进行竞争性ELISA试验，我们在位于分子C末端区域的抑制蛋白的一个主要免疫原性位点上确定了MS患者血清中抗体的识别位点。我们认为，与β-抑制蛋白或抑制蛋白反应的循环抗体的存在可能与MS的进展过程有关。
