The immune cell transcriptome is modulated by vitamin D₃ supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial

Wei Zhen Yeh¹, Melissa Gresle², Rodney Lea³, Bruce Taylor⁴, Robyn M Lucas⁵, Anne-Louise Ponsonby⁶, Deborah Mason⁷, Julie Andrew⁸, Hamish Campbell⁹, Julia Morahan⁹, Sandeep Sampangi², Maria Pia Campagna², Jim Stankovich¹⁰, Anneke Van der Walt², Vilija Jokubaitis², Helmut Butzkueven¹¹

Affiliations

¹ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia. Electronic address: wei.yeh@monash.edu.
² Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
³ School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia; Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
⁴ Royal Hobart Hospital, Department of Neurology, Hobart, Australia; University of Tasmania, Menzies Institute for Medical Research, Hobart, Australia.
⁵ Australian National University, National Centre for Epidemiology and Population Health, Canberra, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, Early Brain Division, Parkville, Australia; University of Melbourne, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
⁷ Christchurch Hospital, Christchurch, New Zealand; New Zealand Brain Research Institute, Christchurch, New Zealand.
⁸ Neuroscience Trials Australia, Heidelberg, Australia.
⁹ MS Australia, North Sydney, Australia.
¹⁰ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
¹¹ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia; MSBase Foundation, Melbourne, Australia. Electronic address: helmut.butzkueven@monash.edu.

PMID: 38479439
DOI: 10.1016/j.clim.2024.110183

Randomized Controlled Trial

The immune cell transcriptome is modulated by vitamin D₃ supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial

Wei Zhen Yeh et al. Clin Immunol. 2024 May.

. 2024 May:262:110183.

doi: 10.1016/j.clim.2024.110183. Epub 2024 Mar 11.

Authors

Affiliations

¹ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia. Electronic address: wei.yeh@monash.edu.
² Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
³ School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia; Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
⁴ Royal Hobart Hospital, Department of Neurology, Hobart, Australia; University of Tasmania, Menzies Institute for Medical Research, Hobart, Australia.
⁵ Australian National University, National Centre for Epidemiology and Population Health, Canberra, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, Early Brain Division, Parkville, Australia; University of Melbourne, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
⁷ Christchurch Hospital, Christchurch, New Zealand; New Zealand Brain Research Institute, Christchurch, New Zealand.
⁸ Neuroscience Trials Australia, Heidelberg, Australia.
⁹ MS Australia, North Sydney, Australia.
¹⁰ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
¹¹ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia; MSBase Foundation, Melbourne, Australia. Electronic address: helmut.butzkueven@monash.edu.

PMID: 38479439
DOI: 10.1016/j.clim.2024.110183

Abstract

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D₃ supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D₃ or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D₃ supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D₃ supplementation on immune gene expression.

Keywords: Clinically isolated syndrome; First demyelinating event; Gene expression; Multiple sclerosis; Vitamin D.

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Conflict of interest statement

Declaration of competing interest WZY received research support from MS Australia, the Australian Government Research Training Program and the Monash University Postgraduate Publications Award during the conduct of the study. BT received funding for travel and speaker honoraria from Bayer Schering Pharma, CSL Australia, Biogen and Novartis, and has served on advisory boards for Biogen, Novartis, Roche and CSL Australia. AVdW has served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche; she has received speaker's honoraria and travel support from Novartis, Roche, Biogen and Merck; she receives grant support from the National Health and Medical Research Council of Australia and MS Australia. VJ received conference travel support from Merck and Roche and speaker's honoraria from Biogen and Roche outside of the submitted work; she receives research support from the Australian National Health and Medical Research Grant and MS Australia. HB has received institutional (Monash University) funding from Biogen, F. Hoffmann-La Roche Ltd., Merck, Alexion, CSL, and Novartis; has carried out contracted research for Novartis, Merck, F. Hoffmann-La Roche Ltd. and Biogen; has taken part in speakers' bureaus for Biogen, Genzyme, UCB, Novartis, F. Hoffmann-La Roche Ltd. and Merck; has received personal compensation from Oxford Health Policy Forum for the Brain Health Steering Committee. Other authors report no relevant competing interests.

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The immune cell transcriptome is modulated by vitamin D₃ supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial

Affiliations

The immune cell transcriptome is modulated by vitamin D₃ supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial

Authors

Affiliations

Abstract

Conflict of interest statement

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LinkOut - more resources

Medical

Research Materials