Environmental and behavioural risk factors in MS

Summary

Using the two largest and most comprehensive studies of MS onset and disease, this research will investigate a number of environmental and behavioural factors for their role in MS. Environmental factors to be included are vitamin D and UV exposure, smoking, alcohol, coffee intake, immunisations, any other concurrent disorders, and exposure to chemicals and domestic animals.

Dr Simpson will incorporate information about past infections with Epstein-Barr virus and human herpes virus 6. The study will also comprise a number of genetic risk factors for MS. This information will be correlated with aspects of early and established MS such as conversion to clinically definite disease, relapse rates, levels of disability and changes to disability over time, and lesion volume and changes to lesion load over time as measured by magnetic resonance imaging (MRI). This material will be used to create an algorithm that could be used in the clinical setting to predict disease activity and course for people with MS.

Progress to Date

Dr Simpson’s initial analyses have utilised the NHMRC-funded Tasmanian MS Longitudinal Study cohort to explore whether a range of factors may be associated with increased risk of relapse or the progression of disability. The Longitudinal study is a highly valuable long-term data resource with detailed information on relapses, disability, MRI scans, lifestyle, immune function, virology, and genetics.

They identified potentially important factors to include domestic animal exposure, infections, immunisation and lipids. Ongoing analyses are investigating any relationship between alcohol intake and the risk of relapse or worsening disability.

In a recent publication in the Journal of Neurology, Neurosurgery, and Psychiatry, Dr Simpson and colleagues found that increased production of an immune molecule (cytokine) called IFN-γ was associated with a higher risk of relapse over time. In contrast, the researchers found that higher production of another cytokine, called TNF-α, was associated with a lower relapse risk. In addition, the researchers found that several environmental and genetic factors may have an important influence on the cytokine production and the risk of relapse. In particular, levels of Vitamin D, sun exposure, season (summer), medication type, and genetic profiles were all shown to interact with IFN-γ or TNF-α production to influence inflammatory activity and therefore risk of relapse in individuals with MS.

Dr Simpson has also published a number of studies looking at other environmental factors and MS course, including lipid profiles. In a series of papers, Dr Simpson has shown that an adverse lipid profile was associated with high levels of MS disability and disease progression but was not associated with relapses in MS. Recent papers have looked at specific interactions between genes and environmental factors known to be of relevance in MS.

Further work will use another important longitudinal cohort, the Ausimmune Longitudinal Study (AusLong), to replicate the findings of the previous studies, including studying the association between factors such as vitamin D, infection, and substance use, with the risk of developing MS and having future relapses.

Publications

Zhou Y, Taylor B, van der Mei I, Stewart N, Charlesworth J, Blizzard L, Ponsonby AL, Dwyer T, Pittas F, Simpson S Jr. Genetic variation in PBMC-produced IFN-γ and TNF-α associations with relapse in multiple sclerosis. J Neurol Sci. 2015 Feb 15; 349(1-2):40-4.
Simpson S Jr, Taylor B, Burrows J, Burrows S, Dwyer DE, Taylor J, Ponsonby AL,
Blizzard L, Dwyer T, Pittas F, van der Mei I. EBV & HHV6 reactivation is infrequent and not associated with MS clinical course. Acta Neurol Scand. 2014 Nov; 130(5):328-37.
Lin R, Taylor BV, Charlesworth J, van der Mei I, Blizzard L, Stewart N, Ponsonby AL, Dwyer T, Pittas F, Simpson S Jr. Modulating effects of WT1 on interferon-β-vitamin D association in MS. Acta Neurol Scand. 2015 Apr;131(4):231-9.
Tettey P, Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Dwyer T, Kostner K, van der Mei I. Adverse lipid profile is not associated with relapse risk in MS: results from an observational cohort study. J Neurol Sci. 2014 May 15; 340(1-2):230-2.
Tettey P, Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Dwyer T, Kostner K, van der Mei I. An adverse lipid profile is associated with disability and progression in disability, in people with MS. Mult Scler. 2014 Nov; 20(13):1737-44.
Simpson Jr. SL & Stewart N, van der Mei I, Otahal P, Charlesworth J, Ponsonby A-L, Blizzard L, Dwyer T, Pittas F, Gies P, Taylor BV. “Stimulated PBMC-produced IFN-γ and TNF-α significantly modulate relapse risk in multiple sclerosis.” Journal of Neurology, Neurosurgery & Psychiatry
Zhou Y, Simpson Jr. SL, Holloway AF, Charlesworth J, van der Mei I, Taylor BV. “The potential role of epigenetic modifications in the heritability of multiple sclerosis.” Multiple Sclerosis Journal. Feb 2014; 20(2); 135-40.
Lin R, Taylor BV, Simpson Jr. SL, Charlesworth J, Ponsonby A-L, Pittas F, Dwyer T, van der Mei I. “Novel modulating effects of PKC family genes on the relationship between serum vitamin D and relapse in multiple sclerosis.” Journal of Neurology, Neurosurgery, and Psychiatry. doi: 10.1136/jnnp-2013-305245.
Taylor BV, Palmer A, Simpson Jr. SL, Lucas R, NZMSPS study group, Simmons RD. “Assessing possible selection bias in a national voluntary MS longitudinal study in Australia.” Multiple Sclerosis Journal. April 2013; 19(12); 1627 – 31.
Palmer AJ, Hitchens PL, Simpson Jr. SL, O’Leary B, Colman S, Taylor BV. “A novel method for calculating prevalence of multiple sclerosis in Australia.” Multiple Sclerosis Journal. April 2013; 19(13); 1704 – 11.
Knippenberg S, Damoiseaux J, Boi Y, Hubberts R, Taylor BV, Ponsonby A-L, Dwyer T, Simpson Jr. SL, van der Mei I. “Higher levels of reported sun exposure, and not vitamin D status, are associated with less depressive symptoms and fatigue in multiple sclerosis,” Acta Neurologica Scandinavica. 2014; 129(2): 123-131.