How vitamin D affects the immune system in MS

Dr Wei Yeh

Alfred Health and Monash University, VIC

| Better treatments | Immunology | Scholarship | 2020 | Investigator Led Research |
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Summary

MS is one of the most common neurological causes of disability among young adults. Living further away from the equator is associated with less exposure to UV from the sun and less vitamin D production, and is also linked to a higher rate of MS. These and other findings support a significant role for vitamin D in the development of MS. Dr Wei Yeh aims to determine the effects that vitamin D has on immune cells in people with MS, and how this is different to people without MS. This will shed further light on the role of vitamin D in MS risk and will help determine ways to prevent the development of MS.

Additionally, Dr Yeh will also investigate factors that might influence the risk of relapses during pregnancy. Previous studies have shown a reduced risk of relapse during pregnancy. Dr Yeh will use data from MSBase, a large international registry of people with MS, to find factors that predict relapse in pregnancy. These findings will help guide what to do in the clinic to minimise the chances of a relapse during pregnancy.

Progress to Date

Vitamin D deficiency is recognised as a risk factor for the development of MS. However, the effects of vitamin D on the immune system are not well understood, either in people with MS or people without MS. Dr Yeh published a manuscript reviewing what is currently known about the immune effects and the therapeutic potential of vitamin D, and what are the gaps in our knowledge. This project aims to fill some of these gaps, and better understand the effects of vitamin D on immune cells in the body.

Dr Yeh first investigated whether there was any relationship between vitamin D levels in the blood, and the extent to which individual genes are switched on (or “gene expression”) in different types of immune cells. In individuals without MS, they found vitamin D levels were associated with expression of genes involved in inflammation. Dr Yeh will next investigate whether there are any differences in response to vitamin D between those people with and without MS.

Dr Yeh also investigated gene expression in people who have had a first neurological episode (or first “demyelinating event”) that may lead on to become MS. He looked at the effect of taking vitamin D supplements for 3 months in these people, as part of the PrevANZ study.  In people taking high doses of vitamin D, the team found changes to pathways involved in immune function, inflammation and other specific cellular processes. These observations support the role of vitamin D in influencing the immune system and will help inform the results of the PrevANZ study.

As most patients with MS are women, understanding how MS activity changes during pregnancy is important. Dr Yeh used data from the MSBase International MS Registry, including approximately 2000 pregnancies. The team observed that women with more active MS or who were treated with modern therapies, natalizumab (Tysabri”) and fingolimod (Gilenya), were at an increased risk of relapse if they stopped their therapy during pregnancy. Continuing natalizumab treatment during pregnancy reduced the rates of MS relapse, and starting natalizumab again after birth protected women against the increase rate of relapse that usually occurs in that period. These findings will help MS neurologists and women with MS to better plan their treatments to minimise the risks of relapse around the time of pregnancy. Find out more about these findings here.

Over the next year, Dr Yeh will continue to study the differences in the immune response to vitamin D between people with MS and without MS, and will complete further studies of the vitamin D response in participants from the PrevANZ study.

Publications

Yeh WZ, Widyastuti PA, Van der Walt A, Stankovich J, Havrdova E, Horakova D, Vodehnalova K, Ozakbas S, Eichau S, Duquette P, Kalincik T, Patti F, Boz C, Terzi M, Yamout BI, Lechner-Scott J, Sola P, Skibina OG, Barnett M, Onofrj M, Sá MJ, McCombe PA, Grammond P, Ampapa R, Grand'Maison F, Bergamaschi R, Spitaleri DLA, Van Pesch V, Cartechini E, Hodgkinson S, Soysal A, Saiz A, Gresle M, Uher T, Maimone D, Turkoglu R, Hupperts RM, Amato MP, Granella F, Oreja-Guevara C, Altintas A, Macdonell RA, Castillo-Trivino T, Butzkueven H, Alroughani R, Jokubaitis VG; MSBase Study Group. Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis. Neurology. 2021 Apr 20:10.1212/WNL.0000000000012084. doi: 10.1212/WNL.0000000000012084. Epub ahead of print. PMID: 33879599.

Yeh WZ, Gresle M, Jokubaitis V, Stankovich J, van der Walt A, Butzkueven H. Immunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis. Br J Pharmacol. 2020 Sep;177(18):4113-4133. doi: 10.1111/bph.15201. Epub 2020 Aug 5. PMID: 32668009; PMCID: PMC7443468.

Updated: 16 May 2021

Updated: 21 January, 2020

Stages of the research process

Fundamental laboratory
Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline: 10+ years
Translational
Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline: 5+ years
Clinical Studies
and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline: 1-5 years

Investigator

  • Dr Wei Yeh

Grant Awarded

  • Postgraduate Scholarship

Total Funding

  • $42,560

Duration

  • 2 years

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How vitamin D affects the immune system in MS