Yeh, Wei ZhenGresle, MelissaLea, RodneyTaylor, BruceLucas, Robyn M.Ponsonby, Anne LouiseMason, DeborahAndrew, JulieCampbell, HamishMorahan, JuliaSampangi, SandeepCampagna, Maria PiaStankovich, JimVan der Walt, AnnekeJokubaitis, VilijaButzkueven, Helmut2026-06-112026-06-111521-6616PubMed:38479439https://hdl.handle.net/1885/733810227Vitamin 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.This work was supported by an MS Australia Postgraduate Scholarship, No. 19–0735; Australian Government Research Training Program Scholarship; Monash University Postgraduate Publications Award; and, MS Australia incubator grant. These bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.enPublisher Copyright: © 2024 The Author(s)Clinically isolated syndromeFirst demyelinating eventGene expressionMultiple sclerosisVitamin D202410.1016/j.clim.2024.11018385187988749