The pathogenesis of multiple sclerosis

Abstract

The pathogenesis of multiple sclerosis (MS) involves both genetic-susceptibility and, at least, three sequential environmental-events. The first environmental-event is a maternal-factor, which acts near birth. The second acts subsequently but prior to approximately age 15 years and the third acts long after these first two events have already taken place. Two environmental-events strongly implicated in MS-pathogenesis are Vitamin D deficiency and Epstein-Barr viral (EBV) infection. These factors seem well-suited to the first two environmental-events in this causal chain. If this notion is correct, it is likely that interrupting either of these factors (e.g. the timely supplementation of Vitamin D or the development of an EBV vaccine might be simple and effective methods for achieving primary disease prevention. In addition to these environmental-events, genetic factors are both crucial and complex. More than 110 genomic-regions have now been associated with MS-susceptibility and only a very small fraction of the population is genetically-susceptible. However, the actual genes involved are much more poorly defined than is often thought. For example, it turns out that the well-established association with the DRB1∗1501 allele on chromosome 6, is, likely, not due to this allele itself but, rather, to something else that resides on the SNP-haplotype, which usually harbors this allele. Also, despite women being the large majority of MS patients, men are more likely to be genetically-susceptible. Nevertheless, women are more responsive to the changing environmental-exposures, which have occurred recently; thereby accounting for the changes in sex-ratio and MS-prevalence in women, which have been found in many regions.