Environmental risk factors for multiple sclerosis. Part I: The role of infection

Abstract

Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families and the sharp decline in risk with increasing genetic distance, it cannot fully explain the geographic variations in MS frequency and the changes in risk that occur with migration. Epidemiological data provide some support for the "hygiene hypothesis," but with the additional proviso for a key role of Epstein-Barr virus (EBV) in determining MS risk. We show that whereas EBV stands out as the only infectious agent that can explain many of the key features of MS epidemiology, by itself the link between EBV and MS cannot explain the decline in risk among migrants from high to low MS prevalence areas. This decline implies that either EBV strains in low-risk areas have less propensity to cause MS, or that other infectious or noninfectious factors modify the host response to EBV or otherwise contribute to determine MS risk. The role of infectious factors is discussed here; in a companion article, we will examine the possible role of noninfectious factors and provide evidence that high levels of vitamin D may have a protective role, particularly during adolescence. The primary purpose of these reviews is to identify clues to the causes of MS and to evaluate the possibility of primary prevention.

Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis

“…Another explanation is the "hygiene hypothesis" [80] , which states that the high rates of infection in third world countries explain the relatively low incidence of MS near the equator in comparison with near the 2 poles [80] . This is further supported by the experimental data from animal studies, which show that helminth infections protect from experimental autoimmune diseases, including EAE [81] .…”

Intrathecal immune responses to EBV in early MS

“…Both genetic [1] and environmental [2] factors are thought to be involved in MS. Among the latter, the g-herpesvirus EBV has been repeatedly associated with this disease [2][3][4].…”

“…Both genetic [1] and environmental [2] factors are thought to be involved in MS. Among the latter, the g-herpesvirus EBV has been repeatedly associated with this disease [2][3][4]. Large seroepidemiological studies [5][6][7][8] and cellular immune response assessments [9][10][11][12] have demonstrated enhanced EBV-specific immune responses in the blood of MS patients.…”

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

“…It is accompanied by a wide continuum of signs and symptoms with a profound effect on the communication between nerve cells inside the brain and spinal cord [1]. Although there is incomplete understanding of the basic mechanisms behind MS pathogenesis, evidence suggests heterogeneous etiologies of MS, implying the role of multiple environmental factors in its course and development [3][4][5].…”