Multiple Sclerosis: A Coordinated Immunological Attack against Myelin in the Central Nervous System

Abstract

Multiple sclerosis (MS) is the most common autoimmune disease involving the nervous system. In the United States ∼250,000 individuals suffer from MS. The first clinical signs of MS typically begin in young adulthood, and women with the disease outnumber men 2:1. The cause of the disease is unknown, but genetic factors are important. The concordance rate among monozygotic twins is 30%, a 10-fold increase over dizygotic twins or first-degree relatives (Ebers et al. 1986; Ebers et al. 1995). The higher incidence rate among monozygotic twins emphasizes the importance of genetic factors, but the discordance rate of 70% among identical twins illuminates the role of nongenetic factors on disease penetrance. The fact that the prevalence of MS among nonbiological first-degree relatives of MS index cases is similar to that in the general population strongly supports a genetic basis for familial clustering (Ebers et al. 1995). Among genetic factors, HLA class II genes exert an influence, with HLA DR2 carrying a 4-fold relative risk for northern European caucasoids (Altmann et al. 1991; Oksenberg et al. 1993a; Oksenberg et al. 1993b). Geography plays an interesting role in determining susceptibility to MS. Among white populations, the prevalence of MS is highest in the temperate regions of the world (Kurtzke 1983). Migration from a location of high disease incidence to a location of low disease incidence after the age of 15 years carries with it the risk associated with the location where one dwelled during the first 15 years, while migration before the age of 15 years carries the risk associated with the immigrant's destination (Kurtzke 1983).