ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions   (#222)

Samantha P.L Law 1 , Prudence N Gatt 1 , Stephen D Schibeci 1 , Fiona C McKay 1 , Steve Vucic 1 , Prue Hart 2 , Scott N Byrne 1 , David Brown 1 , Graeme J Stewart 1 , Christopher Liddle 3 , Grant P Parnell 1 , David R Booth 1
  1. Centre for Immunology and Allergy Research, Westmead Institute for Medican Research, Sydney, NSW, Australia
  2. Telethon Kids Institute, Perth Children's Hospital, Perth, WA, Australia
  3. Westmead Institute for Medical Research, Sydney, NSW, Australia

Various genetic and epidemiological evidence support the importance of vitamin D in multiple sclerosis (MS). However, use of cholecalciferol (25-OH-D3) is ineffective in improving disease despite evidence of increased vitamin D serum levels [1-2]. Utilising previously identified vitamin D responsive MS risk genes (VDRMs), we aimed to evaluate if they could be used as markers of vitamin D response in immune cells.

Peripheral blood mononuclear cells (PBMCs) from healthy controls (n=10) and multiple sclerosis patients treated with dimethyl fumarate (n=10) were isolated and treated with and without 25-OH-D3. Cells were further treated with and without (homeostatic condition) a range of inflammatory stimuli targeting different immune cell subsets: TNF-α (monocytes), CD3/CD28 Activation beads (T cells), CD40 Ligand (B cells) and IFN-β (NK Cells). After 24hr, cells were harvested for gene expression analysis of the VDRMs.

VDRMs genes were altered in PBMCs treated with vitamin D in both inflammatory and homeostatic conditions, particularly expression of CYP24A1. Between healthy controls and MS patients, similar responses were observed in relation to vitamin D response, however, addition of vitamin D counteracted the initial lower expression of risk genes observed in MS patients.

 From this study, there is potential for CYP24A1 and other VDRMs to be utilised as biological markers to assess immunological responses to vitamin D.

  1. McLaughlin L, Clarke L, Khalilidehkordi E, Butzkueven H, Taylor B, Broadley SA. Vitamin D for the treatment of multiple sclerosis: a meta-analysis. J Neurol. 2018;265:2893–905
  2. Zheng C, He L, Liu L, Zhu J, Jin T. The efficacy of vitamin D in multiple sclerosis: a meta-analysis. Mult Scler Relat Disord. 2018;23:56–61