Fujihara Kazuo
Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine.
Nihon Rinsho. 2008 Jun;66(6):1087-91.
Recent findings on the etiology and pathogenesis of multiple sclerosis (MS) and neuromyelitis optica (NMO) were reviewed. As new MS-susceptibility genes, IL-7Ralpha and IL-2Ralpha genes were identified. Among environmental factors, Epstein-Barr virus, vitamin D and smoking appear to play a role in developing MS. As opposed to previous reports on the lesion heterogeneity, a recent study showed antibody-, complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in MS. Clinical trials of monoclonal antibodies demonstrated that targeting such immune molecules as CD52, CD25, VLA-4 and CD20, is therapeutically effective. Aquaporin-4 (AQP4) antibody is a diagnostically useful biomarker of NMO, and a recent study revealed severe astrocytic damage in NMO probably caused by AQP4-targeting is a pathological finding distinct from that in MS.
对多发性硬化症(MS)和视神经脊髓炎(NMO)的病因及发病机制的最新研究结果进行了综述。作为新的MS易感基因,白细胞介素-7受体α(IL-7Rα)基因和白细胞介素-2受体α(IL-2Rα)基因被识别出来。在环境因素中,爱泼斯坦-巴尔病毒、维生素D和吸烟似乎在MS的发病过程中起作用。与之前关于病变异质性的报道相反,最近一项研究表明,抗体介导、补体介导的髓鞘吞噬作用是MS脱髓鞘的主要机制。单克隆抗体的临床试验表明,靶向CD52、CD25、VLA-4和CD20等免疫分子具有治疗效果。水通道蛋白-4(AQP4)抗体是NMO诊断中有用的生物标志物,最近一项研究表明,NMO中严重的星形胶质细胞损伤可能由靶向AQP4引起,这是一种与MS不同的病理表现。