Molecular mechanism underlying the impact of vitamin D on disease activity of MS

Abstract : Objective: Some previous studies suggest modest to strong effects of 25-hydroxyvitamin D (25(OH)D) on multiple sclerosis (MS) activity. The objective of this study was to explore the mechanistic rationale that may explain poten-tial clinical effects of 25(OH)D. Methods: This study measured serum 25(OH) D levels and global gene expression profiles over a course of up to 2 years in patients starting treatment with interferon beta-1b (IFNB-1b) after a clinically isolated syndrome. MS disease activity was assessed by the number of gadolin-ium-enhancing lesions present on repeated magnetic resonance imaging (MRIs). Results: The number of gadolinium-enhancing lesions was highly sig-nificantly associated with 25(OH)D levels. Conducting various systems-level analyses on the molecular level, multiple lines of evidence indicated that 25 (OH)D regulates expression dynamics of a large gene–gene interaction system which primarily regulates immune modulatory processes modulating MS activ-ity. The vitamin D response element was significantly enriched in this system, indicating a direct regulation of this gene interaction network through the vita-min D receptor. With increasing 25(OH)D levels, resulting regulation of this system was associated with a decrease in MS activity. Within the complex net-work of genes that are regulated by 25(OH)D, well-described targets of IFNB-1b and a regulator of sphingosine-1-phosphate bioavailability were found. The 25(OH)D effects on MS activity were additively enhanced by IFNB-1b. Inter-pretation: Here, we provide mechanistic evidence that an unbalanced 25(OH)D gene expression system may affect MS activity. Our findings support a potential benefit of monitoring and managing vitamin D levels (e.g., through supplemen-tation) in early MS patients treated with IFN-beta-1b.
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Annals of Clinical and Translational Neurology, Wiley, 2014, 1 (8), pp.605 - 617. 〈10.1002/acn3.91〉
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Kassendra Munger, Karl Köchert, Kelly Simon, Ludwig Kappos, Chris Polman, et al.. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Annals of Clinical and Translational Neurology, Wiley, 2014, 1 (8), pp.605 - 617. 〈10.1002/acn3.91〉. 〈inserm-01103106〉

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