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Immune system activity predicts relapse risk in MS

MS Research Australia-funded Research Fellow, Dr Steve Simpson Jr and his colleagues at the Menzies Institute for Medical Research have measured the levels of immune molecules (cytokines) that are produced by white blood cells, and tested their relationship to the frequency of relapse and other environmental factors such as Vitamin D. The study, recently published in the Journal of Neurology, Neurosurgery, and Psychiatry, is part of a larger project aiming to build a model that can predict and explain disease activity and disease course in people with MS.

Blood samples were collected every 6 months over a two and a half year period from 119 people with relapsing remitting MS as part of the NHMRC-funded Tasmanian MS Longitudinal Study. This study is a highly valuable long-term data resource with detailed information on relapses, disability, MRI scans, lifestyle, immune function, virology, and genetics.

In this part of the study, the levels of cytokine molecules, produced by immune cells isolated from the blood of people with MS, were measured and compared with the occurrence of relapses. Cytokines are molecules produced by immune cells that can either activate (pro-inflammatory) or calm (anti-inflammatory) other cells of the immune system. A range of environmental and social factors were also taken into account allowing the researchers to begin piecing together a picture of the strongest predictors of future relapses.

Dr Simpson and colleagues found that increased production of a pro-inflammatory cytokine molecule 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. This was particularly important because a relationship between TNF-α and relapse had not been reported in any previous studies.

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.

These results provide an important insight into the very complex interactions between genetic, environmental and behavioural factors that are likely to contribute to the disease course of MS, and how developing new medications that target these cytokines may help treat MS. Future work by Dr Simpson and his team will also test relationships between other potentially important disease factors, with the goal of creating a tool that could be used in the clinical setting to predict disease activity and disease course for people with MS. This type of tool will be an extremely useful step towards helping to determine the most appropriate individualised treatment protocols based on clinical symptoms and disease markers in the blood.

Click here for more information on Dr Simpson’s Fellowship project. Funding for the measurement of vitamin D levels in this study was provided by a previous grant from the Trish MS Research Foundation.

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Immune system activity predicts relapse risk in MS