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The initiation and prevention of multiple sclerosis

Abstract

Although strong genetic determinants of multiple sclerosis (MS) exist, the findings of migration studies support a role for environmental factors in this disease. Through rigorous epidemiological investigation, Epstein–Barr virus infection, vitamin D nutrition and cigarette smoking have been identified as likely causal factors in MS. In this Review, the strength of this evidence is discussed, as well as the potential biological mechanisms underlying the associations between MS and environmental, lifestyle and dietary factors. Both vitamin D nutrition and cigarette smoking are modifiable; as such, increasing vitamin D levels and smoking avoidance have the potential to substantially reduce MS risk and influence disease progression. Improving our understanding of the environmental factors involved in MS will lead to new and more-effective approaches to prevent this disease.

Key Points

  • The aetiology of multiple sclerosis (MS) is multifactorial, with both genetic and environmental factors contributing to the risk of disease

  • Strong evidence supports a causal role for Epstein–Barr virus (EBV) infection in the initiation of MS

  • Primary infection with EBV and a history of infectious mononucleosis increase an individual's risk of MS, with elevation of antibody titres to EBV nuclear antigen being observed before disease onset

  • Longitudinal studies of supplementary vitamin D intake and pre-onset serum levels of 25-hydroxyvitamin D support a protective effect of vitamin D on MS risk

  • Cigarette smoking has been associated with an increased risk of MS in men and women, and changes in smoking patterns may partially explain the increasing female:male ratio in MS

  • Our understanding of how EBV infection, vitamin D metabolism, and cigarette smoking influence MS risk are limited, and further studies are required

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Figure 1: Time of EBV seroconversion and MS.
Figure 2: Relative risk of multiple sclerosis based on levels of EBNA IgG antibody titres.
Figure 3: Mechanisms by which EBV infection might contribute to development of MS.
Figure 4: Effects of vitamin D supplementation on immune responses in human trials.
Figure 5: Link between smoking behaviour and MS risk in Canada.

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Acknowledgements

This work was funded by grants R01 NS046635, R01 NS073633 and R01 NS071082 from the NIH. The authors thank L. Unger, Harvard School of Public Health, for her technical assistance in preparing this manuscript.

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The authors contributed equally to researching data for the article, providing substantial contribution to discussion of the content, writing the article, and to review and/or editing of the manuscript before submission.

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Correspondence to Alberto Ascherio.

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Ascherio, A., Munger, K. & Lünemann, J. The initiation and prevention of multiple sclerosis. Nat Rev Neurol 8, 602–612 (2012). https://doi.org/10.1038/nrneurol.2012.198

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