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Sittard, Netherlands

Smolders J.,Maastricht University | Smolders J.,Academic Center Limburg
Autoimmune Diseases | Year: 2011

The last years, many studies reported associations between correlates of vitamin D exposure and several correlates of multiple sclerosis (MS) disease activity. This review discusses studies on vitamin D status, Expanded Disability Status Scale (EDSS) score, and relapse activity of MS. Furthermore, several considerations for intervention studies on vitamin D supplementation in MS are provided. Copyright © 2011 Joost Smolders. Source

Smolders J.,Group 47 | Smolders J.,Maastricht University | Peelen E.,Maastricht University | Peelen E.,transnational University of Limburg | And 5 more authors.
Multiple Sclerosis Journal | Year: 2014

Background: A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). Objectives: The purpose of this study was to explore whether there is an association between MS and DBP. Methods: We compared DBP concentrations in blood samples of controls (n = 30) and subjects with relapsing-remitting MS (RRMS) during remission (n = 29) and relapse (n = 15). Furthermore, we explored correlations of DBP with 25- hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D levels (1,25(OH)2D), and the effect of high-dose vitamin D3 supplementation on DBP levels in RRMS patients (n = 15). Results: DBP-concentration did not differ between the sub-groups measured, and there was no correlation between DBP and vitamin D metabolite concentration within the physiological range. Upon supplementation of high doses vitamin D3, DBP concentration remained unaltered. After supplementation, serum 1,25(OH)2D(R = 0.517, p = 0.049), but not 25(OH)D, correlated positively with DBP. Conclusions: We found no association between DBP, MS, and vitamin D status within the physiological range. After high - dose vitamin D supplementation, DBP concentrations may be relevant for vitamin D metabolism. © The Author(s) 2013. Source

Rolf L.,Maastricht University | Damoiseaux J.,Maastricht University | Hupperts R.,Maastricht University | Huitinga I.,Netherlands Institute for Neuroscience | Smolders J.,Academic Center Limburg
Autoimmunity Reviews | Year: 2016

Sex-steroids, corticosteroids and vitamin D3-derived molecules have all been subject to experimental studies and clinical trials in a plethora of autoimmune diseases. These molecules are all derived from cholesterol metabolites and are ligands for nuclear receptors. Ligation of these receptors results in direct regulation of multiple gene transcription involved in general homeostatic and adaptation networks, including the immune system. Indeed, the distinct ligands affect the function of both myeloid and lymphoid cells, eventually resulting in a less pro-inflammatory immune response which is considered beneficial in autoimmune diseases. Next to the immune system, also the central nervous system is prone to regulation by these nuclear receptor ligands. Understanding of the intricate interactions between sex-steroids, corticosteroids and vitamin D3 metabolites, on the one hand, and the immune and central nervous system, on the other hand, may reveal novel approaches to utilize these nuclear receptor ligands to full extent as putative treatments in multiple sclerosis, the prototypic immune-driven disease of the central nervous system. © 2016 Elsevier B.V. Source

Rolf L.,Maastricht University | Rolf L.,Academic Center Limburg | Muris A.-H.,Maastricht University | Muris A.-H.,Academic Center Limburg | And 3 more authors.
Annals of the New York Academy of Sciences | Year: 2014

Vitamin D seems to be implicated in the pathophysiology of autoimmune disorders as a natural immune modulator. Beneficial effects of vitamin D have been associated with different cells of the immune system; however, thus far, B cells seem to be somewhat neglected. In this paper, we describe the possible direct effects of vitamin D on B cells, with a focus on antibody production and the more recently identified regulatory B (Breg) cells. B cells upregulate the vitamin D receptor (VDR) upon activation. Furthermore, due to regulated expression of the metabolizing enzymes CYP27B1 and CYP24A1, B cells have the potential to control the local availability of active vitamin D. B cells, therefore, may participate in vitamin D-mediated immune homeostasis, including plasma cell generation. Whether or not other B cell subsets, such as Breg cells, are equally responsive to vitamin D remains to be established. © 2014 New York Academy of Sciences. Source

Peelen E.,Maastricht University | Peelen E.,Academic Center Limburg | Damoiseaux J.,Maastricht University | Muris A.-H.,Maastricht University | And 7 more authors.
Molecular Immunology | Year: 2015

The NLRP3 inflammasome is a macromolecular complex importantly involved in IL-1β processing. A role for this has been described in multiple sclerosis (MS). One mechanism by which IL-1β might be involved in MS is by inducing pathogenic Th17 cells, i.e. GM-CSF+ Th17 cells. In the present study, we show that expression of the inflammasome related genes, NLRP3, caspase-1, IL-1β and the IL-1β/IL-1Ra ratio, was increased in PBMC from MS patients compared to healthy controls (HC). However, in an in vitro inflammasome activity assay with PBMC, IL-1β protein secretion and the IL-1β/IL-1Ra protein ratio were similar in MS patients and HC. Th cells cultured in the presence of supernatant derived from LPS/ATP inflammasome activated PBMC showed increased Th17 and GM-CSF+ Th17 cell frequencies in HC and MS patients and decreased anti-inflammatory IL-10+Th cell frequency in HC compared to Th cells cultured in the presence of control supernatant. Moreover, addition of the immune modulator calcitriol to the former condition resulted in reduced frequencies of Th17 and GM-CSF+Th17 cells, and also of IL-10+ Th cells. Evidently, our data indicate that inflammasome activity can skew the Th cell population toward a more pro-inflammatory composition, an effect that might be inhibited by vitamin D, and that might be importantly involved in inflammation within the central nervous system. © 2014 Elsevier Ltd. Source

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