Etiology And Epidemiology

The etiology of MS is unknown, but evidence suggests that genetic, environmental, and immunologic factors and infectious agents may be involved. Currently, MS is presumed to be an autoimmune disease that develops in genetically susceptible individuals upon activation by some unknown environmental trigger. Several risk factors have been associated with MS. Tobacco smoking significantly increases the odds of developing MS.2 So do other lifestyle factors, such as drinking coffee and alcohol.3 Women are two to three times more likely to develop MS than men, and Caucasians, particularly those of Northern European descent, are more likely to develop MS than other ethnic groups. Individuals living at northern latitudes are also at increased risk, suggesting a possible link with vitamin D and sun exposure. In addition, migration from one geographic area to another changes an individual's risk for MS.

Individuals who move before the age of 15 take on the risk associated with their new geographical location. If an individual migrates after the age of 15, the change in risk is seen in the next generation.3 It is apparent that genetics plays a role in the etiology of MS, given the increased risk of the disease in siblings of individuals with MS, as well as a greater concordance rate in monozygotic compared to dizygotic twins.4 In addition, research indicates that first-degree relatives of individuals with MS have a sevenfold greater than average risk of developing the disease.5 Considerable research is being done to determine the gene or genes that cause(s) susceptibility to MS, and currently, the most consistent finding involves the major histocompatibility complex (MHC), also called the human leukocyte antigen (HLA) system. A specific finding is that a variant in the HLA-DRB1 allele is linked to an increased risk of MS. Most recently, scientists have also found that variants of the gene for the alpha chain of the interleukin (IL)-7 receptor and the gene for the alpha chain of the interleukin IL-2 receptor are associated with an increased risk of MS.6

Numerous infectious agents have also been associated with MS and are currently being investigated. Evidence indicates that infectious mononucleosis caused by the Epstein-Barr virus increases the risk of MS, and that this increased risk persists for at least 30 years after infection.7 Research also shows that infectious mononucleosis in adolescence or young adulthood increases the risk of MS by 2.3-fold.8

Among other findings, Varicella zoster viral DNA has been detected more frequently than average in individuals with MS, and is found in 43.5% of individuals with relapsing-remitting

MS. The results of this same study demonstrated active replication of JC virus and human herpes virus-6 (HHV-6) in the CNS of some individuals with MS.9

Some research also suggests that there is a link between the recombinant hepatitis B vaccine and increased risk of developing MS.10 Studies of pregnancy in women with MS also suggest a role of hormones in the disease. Of the women studied, 75% showed a distinct shift from a Th2 cytokine bias during pregnancy to a Th1 cytokine bias postpartum.11

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