Bansil S, Cook S D, Rohowsky-Kochan C
University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA.
Ann Neurol. 1995 May;37 Suppl 1:S87-101. doi: 10.1002/ana.410370710.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) afflicting approximately 250,000 individuals in the United States. This inflammatory disease has variable clinical manifestations, ranging from a relapsing-remitting course to a chronic progressive disease. Approximately one third of MS patients have chronic progressive disease often leading to severe impairment of mobility, paralysis, poor vision, and disturbances of bladder and bowel function. Although the etiology and pathogenesis remain unknown, accumulating evidence supports the hypothesis that exposure to an as-yet-unidentified infectious agent(s) triggers an aberrant immune response against self nervous tissue in genetically susceptible individuals. The tenfold higher concordance rate for MS in monozygotic twins compared to dizygotic twins, the increased incidence of MS in women compared to men (2:1), and the familial and racial occurrence of MS provide strong evidence that genetic factors influence susceptibility to MS. The major predisposing genes in MS are the human leukocyte antigen (HLA) class II molecules, DR15 and DQw6, molecularly defined as HLA-DRB1, 1501-DQA1 0102-DQB1 0602. In certain ethnic groups, MS susceptibility is more strongly associated with other DR molecules. Environmental factors are also believed to play a role, as suggested by the unique worldwide prevalence, migration effects, and epidemiological studies. Increased serum and cerebrospinal fluid antibody titers to numerous viruses have been reported; however, there have been no confirmed studies detecting viral RNA or antigen in MS brain tissue. At the present time, no known treatment can significantly alter the progression of MS. Based on the postulate that MS is an autoimmune disease associated with abnormalities in immunoregulation, a number of different immunosuppressive and immunomodulating agents have been tested as therapeutic modalities. In this article, we review the circumstantial evidence suggesting that immune system abnormalities are associated with the disease process, and provide an update on current therapies used in MS.
多发性硬化症（MS）是一种中枢神经系统（CNS）的脱髓鞘疾病，在美国约有25万人受其折磨。这种炎症性疾病有多种临床表现，从复发缓解型病程到慢性进展性疾病不等。大约三分之一的MS患者患有慢性进展性疾病，常导致严重的行动能力受损、瘫痪、视力不佳以及膀胱和肠道功能障碍。尽管病因和发病机制尚不清楚，但越来越多的证据支持这样一种假说，即接触一种尚未确定的感染因子会在基因易感个体中引发针对自身神经组织的异常免疫反应。与异卵双胞胎相比，单卵双胞胎中MS的一致性率高出十倍，女性MS发病率高于男性（2:1），以及MS的家族性和种族性发病，都提供了强有力的证据表明遗传因素影响MS易感性。MS中的主要易感基因是人类白细胞抗原（HLA）II类分子DR15和DQw6，分子定义为HLA - DRB1、1501 - DQA1 0102 - DQB1 0602。在某些种族群体中，MS易感性与其他DR分子的关联更为紧密。环境因素也被认为起作用，这从独特的全球患病率、迁移效应和流行病学研究中可以看出。已有报道血清和脑脊液中针对多种病毒的抗体滴度升高；然而，尚未有在MS脑组织中检测到病毒RNA或抗原的确证研究。目前，尚无已知疗法能显著改变MS的病程。基于MS是一种与免疫调节异常相关的自身免疫性疾病这一假设，许多不同的免疫抑制和免疫调节药物已作为治疗方式进行了测试。在本文中，我们回顾了表明免疫系统异常与疾病进程相关的间接证据，并提供了MS当前所用疗法的最新情况。
