calcitriol and Multiple-Sclerosis

The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation.

Topics: Autoimmune Diseases; Cell Proliferation; Cytokines; Genotype; Humans; Immunomodulation; Liver Diseases; Multiple Sclerosis; Polymorphism, Single Nucleotide; Receptors, Calcitriol; T-Lymphocytes; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

Vitamin D is considered to play a role in multiple sclerosis (MS) etiopathogenesis. A polymorphism in the CYP24A1 gene, rs2762943, was recently identified that was associated with an increased MS risk. CYP24A1 encodes a protein involved in the catabolism of the active form of vitamin D. The immunological effects of carrying the rs2762943 risk allele were investigated, as well as its role as genetic modifier.. Serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (1,25(OH). These findings suggest that the CYP24A1 rs2762943 polymorphism plays a more important role in MS susceptibility than in disease prognosis and is associated with lower 1,25(OH)

Topics: Humans; Interferon-gamma; Macrophage Colony-Stimulating Factor; Multiple Sclerosis; Vitamin D; Vitamin D3 24-Hydroxylase; Vitamins

Clear associations have been found between vitamin D deficiency and several autoimmune diseases including multiple sclerosis (MS). However, the benefits of vitamin D supplementation on disease management remain a matter of debate.. Patients with MS (. In both MS and NMOSD, stimulation of PBMCs with 1,25(OH). These findings suggest a beneficial impact of stimulation of PBMCs with vitamin D followed by steroid on the T-cell population. The association between patient serum 25(OH)D

Topics: Adult; B-Lymphocytes; Calcifediol; Case-Control Studies; Cells, Cultured; Dexamethasone; Dietary Supplements; Female; Gene Expression; Glucocorticoids; Humans; Immunologic Memory; Male; Middle Aged; Multiple Sclerosis; Neuromyelitis Optica; T-Lymphocytes; Vitamin D; Vitamins

While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D

Topics: Adult; Antigens; Cell Differentiation; Cryopreservation; Cytokines; Dendritic Cells; Female; Humans; Immune Tolerance; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Multiple Sclerosis; Myelin Sheath; Phenotype; T-Lymphocytes; Vitamin D

Data regarding vitamin D in multiple sclerosis (MS) in Asia are limited. We investigated whether Japanese MS patients show decreased serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and vitamin D-binding protein (DBP) during winter. Mean serum 25(OH)D and 1,25(OH)2D levels were significantly lower in MS patients than in controls. There were no significant differences in serum 25(OH)D, 1,25(OH)2D, and DBP levels between patients or between controls from northern Japan (Hokkaido) and southern Japan (Kyushu). Serum vitamin D levels were low in Japanese MS patients but did not differ in patients from northern and southern Japan.

Topics: Adult; Aged; Analysis of Variance; Disability Evaluation; Ecology; Female; Humans; Japan; Male; Mental Status Schedule; Middle Aged; Multiple Sclerosis; Radioimmunoassay; Seasons; Vitamin D; Vitamin D-Binding Protein; Young Adult

Immunoglobulin-like transcript (ILT) 3 and 4 are inhibitory receptors that modulate immune responses. Their expression has been reported to be affected by interferon, offering a possible mechanism by which this cytokine exerts its therapeutic effect in multiple sclerosis, a condition thought to involve excessive immune activity. To investigate this possibility, we measured expression of ILT3 and ILT4 on immune cells from multiple sclerosis patients, and in post-mortem brain tissue. We also studied the ability of interferon beta, alone or in combination with vitamin D, to induce upregulation of these receptors in vitro, and compared expression levels between interferon-treated and untreated multiple sclerosis patients. In vitro interferon beta treatment led to a robust upregulation of ILT3 and ILT4 on monocytes, and dihydroxyvitamin D3 increased expression of ILT3 but not ILT4. ILT3 was abundant in demyelinating lesions in postmortem brain, and expression on monocytes in the cerebrospinal fluid was higher than in peripheral blood, suggesting that the central nervous system milieu induces ILT3, or that ILT3 positive monocytes preferentially enter the brain. Our data are consistent with involvement of ILT3 and ILT4 in the modulation of immune responsiveness in multiple sclerosis by both interferon and vitamin D.

Topics: Antigen-Presenting Cells; B7 Antigens; Drug Synergism; Humans; Interferon-beta; Membrane Glycoproteins; Monocytes; Multiple Sclerosis; Receptors, Cell Surface; Receptors, Immunologic; Up-Regulation; Vitamin D

Association studies have implicated common variants in the 12q14.1 region containing CYP27B1 in multiple sclerosis (MS). Rare CYP27B1 mutations cause autosomal recessive vitamin D-dependent rickets type 1, and it has recently been reported that heterozygous CYP27B1 mutations are associated with increased MS susceptibility and lower active vitamin D levels. By sequencing CYP27B1 in 134 multiplex families and genotyping the most common variant R389H in 2,608 MS patients and 1,987 controls from Italy and Belgium (a total of 4,729 individuals), we were unable to replicate these observations. These results provide evidence against a major role for CYP27B1 mutations in MS.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adult; Belgium; Case-Control Studies; Computational Biology; Female; Genotype; Humans; Italy; Male; Middle Aged; Multiple Sclerosis; Mutation; Radioimmunoassay; Vitamin D; Young Adult

To determine whether interferon-β (IFN-β) medication use is associated with vitamin D levels and whether the two interact in exerting effects on relapse risk.. In a prospective cohort of 178 persons with clinically definite multiple sclerosis (MS) living in southern Tasmania in 2002-2005, serum 25-hydroxyvitamin D [25(OH)D] was measured biannually, with assessment by questionnaire for relevant factors, including IFN-β treatment.. Subjects reporting IFN-β use had significantly higher mean 25(OH)D than persons who did not (p < 0.001). This was mediated by an interaction between personal sun exposure and IFN-β, with treated persons realizing nearly three times 25(OH)D per hour of sun exposure of persons not on therapy. The association between 25(OH)D and 1,25-dihydroxyvitamin D did not differ by IFN-β therapy (p = 0.82). 25(OH)D was associated with a reduced relapse risk only among persons on IFN-β (p < 0.001). Importantly, IFN-β was only protective against relapse among persons with higher 25(OH)D (hazard ratio [HR] 0.58 [95% confidence interval (CI) 0.35-0.98]), while among 25(OH)D-insufficient persons, IFN-β increased relapse risk (HR 2.01 [95% CI 1.22-3.32]).. In this study, we found that IFN-β therapy is associated with greater production of vitamin D from sun exposure, suggesting part of the therapeutic effects of IFN-β on relapse in MS may be through modulation of vitamin D metabolism. These findings suggest persons being treated with IFN-β should have vitamin D status monitored and maintained in the sufficiency range.. This study provided Class III evidence that IFN-β is associated with reduced risk of relapse, and this effect may be modified by a positive effect of IFN-β on serum 25(OH)D levels.

Topics: Adult; Aged; Body Mass Index; Cohort Studies; Evidence-Based Medicine; Female; Forecasting; Humans; Immunologic Factors; Interferon-beta; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Multiple Sclerosis; Proportional Hazards Models; Prospective Studies; Recurrence; Sunlight; Survival Analysis; Ultraviolet Rays; Vitamin D; Young Adult

The pathogenesis of multiple sclerosis (MS) may involve intrathecal Epstein-Barr virus nuclear antigen-1 (EBNA-1) specific T cells susceptible to modulation by vitamin D. We established EBNA-1 reactive T cell lines from the cerebrospinal fluid (CSF) and blood of three MS patients and cloned EBNA-1 specific CD4+ T cells from two of these. T cell clones from CSF and blood displayed Th1 or Th17 phenotypes and were restricted by HLA-DR molecules, in one patient encoded by the DRB1*0403 or DRB1*1501 haplotypes. 1,25-dihydroxyvitamin D inhibited proliferation and suppressed secretion of IFN-γ and IL-17, irrespective of T cell origin and HLA restriction.

Topics: Adult; Cell Line; Clone Cells; Epitopes, T-Lymphocyte; Epstein-Barr Virus Nuclear Antigens; Female; Humans; Lymphocyte Activation; Male; Multiple Sclerosis; T-Lymphocyte Subsets; Vitamin D; Young Adult

Multiple sclerosis (MS) is a chronic inflammatory disease with an as yet not fully understood etiological background. The geographical distribution of MS is striking with a prevalence that increases with latitude. For this reason, vitamin D deficiency is considered a possible pathogenic co-factor in MS.. To study the role of the vitamin D metabolism in MS, blood samples were taken twice (summer and winter) from 103 patients with MS and 110 healthy controls. Serum concentrations of 25-hydroxyvitamin D (25(OH) D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were measured, and detailed information on disease characteristics and environmental factors that might influence the vitamin D metabolite levels was collected.. Mean serum 25(OH)D and 1,25(OH)(2)D concentrations were significantly higher in summer compared to winter in both patients and controls. Using logistic regression methods, we found that in women for every 10 nmol/L increase of serum 25(OH)D level the odds of MS was reduced by 19% (odds ratio 0.81; 95% confidence interval: 0.69-0.95), suggesting a "protective" effect of higher 25(OH)D serum levels. In addition, also restricted to women, a negative correlation was found between Expanded Disability Status Scale and 25(OH)D levels (r = -0.29, P = 0.020).. Our data suggest that higher circulating levels of 25(OH)D are associated with a lower incidence of MS and MS-related disability in women. This may imply clues to the pathogenesis of the sex difference in risk and to the nature of the environmental factors involved in MS.

Topics: Adult; Environment; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Multiple Sclerosis; Prevalence; Risk Factors; Risk Reduction Behavior; Seasons; Sex Distribution; Vitamin D