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Vitamin D is being increasingly studied in multiple sclerosis (MS). A number of studies have shown that MS patients have lower levels of 25-hydroxyvitamin D as compared to comparator populations, but previous studies in Iran have been conflicting, perhaps due to their small sample size. We performed the largest study to date investigating 25-hydroxyvitamin D levels in Iranian MS patients (n=700) and controls (n=1000). 25-hydroxyvitamin D was measured using a quantitative chemiluminescent immunometric assay. 25-hydroxyvitamin D levels were lower in patients with MS. Over 24% of controls were vitamin D sufficient as compared to 3.4% of patients. Logistic regression showed that for every 1 ng/mL increase in 25-hydroxyvitamin D, the odds for MS decreased (odds ratio=0.87; 95% confidence interval (CI) 0.85-0.88; p<0.001), after adjusting for age and sex. There was no association between 25-hydroxyvitamin D levels and disability scores in MS patients. Iranian Patients with MS have low levels of vitamin D and, where deemed necessary, appropriate supplementation should be given., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The cause of MS remains unknown, but a number of genetic and environmental risk factors, and their interactions, are thought to contribute to disease risk. A substantial evidence base now exists supporting an association between vitamin D and MS, primarily illustrated by a latitudinal gradient of MS prevalence, a month of birth effect, an interaction of vitamin D with MS-associated genes and the fact that high vitamin D levels have been associated with a reduced MS risk in longitudinal prospective work. The association is primarily based on epidemiological studies which renders the more elusive question of whether this association truly represents causation, or indeed reverse causality in the light of a potentially uncharacterised pro-dromal phase of the disease. The prospect of vitamin D supplementation preventing MS is a very attractive notion, but a number of areas of inconsistencies and unanswered questions exist. Most notably, future work will need to establish appropriate dosing, timing and method of vitamin D supplementation in optimising any potential clinical benefit. In this chapter, we discuss the strong epidemiological and growing mechanistic evidence supporting an association between vitamin D and MS, and aim to highlight areas of current debate and where future efforts would be well worth targeting. Given that MS is currently the most common, and a rising, cause of neurological disability in young adults in the Western world, elucidating the relationship between vitamin D and MS is a necessary priority in aiming to further develop therapeutic and preventative strategies against this disease.

Late Epstein-Barr virus infection and hypovitaminosis-D as environmental risk factors in the pathogenesis of multiple sclerosis are gaining great interest. We, therefore, tested for in-vivo interdependence between Epstein-Barr-virus (EBV)-status and 25-hydroxyvitamin D3 (25(OH)D3) -level in healthy young individuals from a United Kingdom (UK) autumn cohort. EBV-load was measured by quantitative polymerase chain reaction and 25(OH)D3 levels by isotope-dilution liquid chromatography-tandem mass spectrometry. This young, healthy UK autumn cohort showed surprisingly low levels of 25(OH)D3 (mean value: 40.5 nmol/L ± 5.02). Furthermore, we found that low 25(OH)D3 levels did not impact on EBV load and anti-EBV nuclear antigen-1 (EBNA-1) titers. However, we observed a correlation between EBV load and EBNA-1 titers. These observations should be of value in the study of the potential relationship between hypovitaminosis-D and EBV-status in the pathophysiology of multiple sclerosis.

Background: Vitamin D deficiency is widely prevalent in India. The association between vitamin D status and multiple sclerosis (MS) has not been previously studied in Indians., Objective: The objective of this paper is to determine whether vitamin D status is associated with MS in India., Methods: In this study 110 MS patients and 108 matched controls were included. Serum 25-hydroxyvitamin D (25(OH)D) was measured in 63 patients in relapse, 77 patients in remission and all controls. Quantity of sun exposure in childhood and body mass index (BMI) were calculated. Patients and controls were genotyped for HLA-DRB1*1501., Results: Patients had significantly lower 25(OH)D levels than matched controls (p = 0.003), and patients in relapse had a significantly lower vitamin D level as compared to those in remission (p = 0.001). Vitamin D deficiency (< 50 nmol/l) was seen in a higher proportion of cases (71.8%) than controls (53.7%) (p = 0.01). Higher quartiles of vitamin D (> 58 nmol/l) showed an inverse relationship with MS (OR = 0.28, CI = 0.11-0.68, p= 0.005). This effect persisted after adjusting for sun exposure., Conclusion: The results of our study indicated that serum 25(OH)D shows an inverse relationship with MS in the Indian population. Reverse causality cannot be excluded.

Observational studies have shown an association between lower vitamin D levels and higher risk of relapse among people with multiple sclerosis (MS). This has raised interest in potential clinical benefits of vitamin D supplementation in the management of MS. The objectives were to examine the effect of vitamin D based interventions on the relative risk of relapse in MS. Any randomised controlled trial assessing the effect on the relative risk of relapse of any formulation or dose of vitamin D, in participants with MS, was eligible. The inverse variance with random effects model in Review Manager 5.1 was used to calculate the odds ratio of relapses in high dose vitamin D treated patients vs. controls. Five studies were published as of September 2012, yielding a total of 129 high-dose vitamin D-treated patients and 125 controls. We found no significant association between high-dose vitamin D treatment and risk of MS relapse (OR 0.98, 95% CI 0.45-2.16). In conclusion, although no significant association between high-dose vitamin D treatment and risk of MS relapses was found, the studies were limited by several methodological limitations. Further larger, more prolonged studies are merited.

Background: Previous studies have suggested that there may be an association between vitamin D deficiency and the risk of developing immune-mediated diseases., Methods: We analyzed a database of linked statistical records of hospital admissions and death registrations for the whole of England (from 1999 to 2011). Rate ratios for immune-mediated disease were determined, comparing vitamin D deficient cohorts (individuals admitted for vitamin D deficiency or markers of vitamin D deficiency) with comparison cohorts., Results: After hospital admission for either vitamin D deficiency, osteomalacia or rickets, there were significantly elevated rates of Addison's disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active hepatitis, celiac disease, Crohn's disease, diabetes mellitus, pemphigoid, pernicious anemia, primary biliary cirrhosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, thyrotoxicosis, and significantly reduced risks for asthma and myxoedema., Conclusions: This study shows that patients with vitamin D deficiency may have an increased risk of developing some immune-mediated diseases, although we cannot rule out reverse causality or confounding. Further study of these associations is warranted and these data may aid further public health studies.

Background: Vitamin D insufficiency has been implicated in autoimmunity. ChIP-seq experiments using immune cell lines have shown that vitamin D receptor (VDR) binding sites are enriched near regions of the genome associated with autoimmune diseases. We aimed to investigate VDR binding in primary CD4+ cells from healthy volunteers., Methods: We extracted CD4+ cells from nine healthy volunteers. Each sample underwent VDR ChIP-seq. Our results were analyzed in relation to published ChIP-seq and RNA-seq data in the Genomic HyperBrowser. We used MEMEChIP for de novo motif discovery. 25-Hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry and samples were divided into vitamin D sufficient (25(OH)D ≥75 nmol/L) and insufficient/deficient (25(OH)D <75 nmol/L) groups., Results: We found that the amount of VDR binding is correlated with the serum level of 25-hydroxyvitamin D (r = 0.92, P= 0.0005). In vivo VDR binding sites are enriched for autoimmune disease associated loci, especially when 25-hydroxyvitamin D levels (25(OH)D) were sufficient (25(OH)D ≥75: 3.13-fold, P<0.0001; 25(OH)D <75: 2.76-fold, P<0.0001; 25(OH)D ≥75 enrichment versus 25(OH)D <75 enrichment: P= 0.0002). VDR binding was also enriched near genes associated specifically with T-regulatory and T-helper cells in the 25(OH)D ≥75 group. MEME ChIP did not identify any VDR-like motifs underlying our VDR ChIP-seq peaks., Conclusion: Our results show a direct correlation between in vivo 25-hydroxyvitamin D levels and the number of VDR binding sites, although our sample size is relatively small. Our study further implicates VDR binding as important in gene-environment interactions underlying the development of autoimmunity and provides a biological rationale for 25-hydroxyvitamin D sufficiency being based at 75 nmol/L. Our results also suggest that VDR binding in response to physiological levels of vitamin D occurs predominantly in a VDR motif-independent manner.

Background: A season of birth effect in immune-mediated diseases (ID) such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB) light exposure and vitamin D status during gestation., Methods: The monthly distribution of births of patients with ID from the UK (n = 115,172) was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient., Results: The distributions of ID births significantly differed from that of the general population (P = 5e-12) with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P < 0.0001) and a trough in October (odds ratio = 0.945, 95% confidence interval = 0.925, 0.966, P < 0.0001). Stratification by disease subtype showed seasonality in all ID but Crohn's disease. The risk of ID was inversely correlated with predicted second trimester UVB exposure (Spearman's rho = -0.49, P = 0.00005) and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003)., Conclusions: The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID.

Vitamin D has been studied for over a century and its functions related to calcium homeostasis are well established. Over the last 30 years or so it has become increasingly clear that it has a wider role in physiology and, importantly, also in disease. Vitamin D deficiency has been linked to multiple sclerosis (MS); however the molecular mechanisms of this association were poorly understood. Recent technological advances have provided major insights as to how vitamin D may exert its role, particularly through the actions of the vitamin D receptor (VDR). In this review we aim to highlight the importance of the interaction between vitamin D and MS associated genes which provide a biological basis for the association between vitamin D and MS risk., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Over the last few years, vitamin D deficiency has emerged as a risk factor for many diseases. Public awareness of the importance of the 'sunshine vitamin' is increasing, however deficiency remains an ongoing problem. Is an awareness of the importance of vitamin D enough to promote healthy people to take supplements or is a different approach required? In this article the importance of vitamin D is discussed and data showing that knowledge of this is not sufficient to encourage people to take supplements are presented.

Background: Multiple sclerosis (MS) is determined by interactions between genes and environment and the influence of vitamin D adequacy has been proposed. Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) levels are genetically influenced. Polymorphisms in vitamin D pathway genes are candidates for association with MS susceptibility., Methods: MS patients (n=1364) and their unaffected first-degree relatives (n=1661) were ascertained through the Canadian Collaborative study. Seventy-one SNPs, across four genes [vitamin D receptor (VDR), 1-alpha-hydroxylase (CYP27B1) enzyme, vitamin D binding protein (DBP), 24-hydroxylase (CYP24)], were genotyped and tested for association with MS susceptibility using TDT in PLINK. Secondary analyses included stratification for HLA-DRB1*15 and parent of origin transmission effects., Results: We found no significant association of vitamin D pathway genes with MS susceptibility after correction for multiple comparisons. However, the VDR Fok1 variant (rs2228570), selected for previously positive associations with MS susceptibility and 25(OH)D levels in MS patients showed marginally distorted transmission in DRB15-negative patients (p=0.03). There was no evidence for differential maternal versus paternal allele transmission., Conclusions: The findings fail to directly connect vitamin D metabolism genes to MS susceptibility, despite a large sample size and comprehensive gene coverage., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). A growing body of evidence supports a role for vitamin D in MS aetiology. Vitamin D binding protein (DBP) is the major plasma carrier of vitamin D metabolites and genetic differences in DBP gene have been found to influence vitamin D levels. We review here evidence supporting a role of DBP in MS. Several recent studies show that DBP levels in the cerebrospinal fluid correlate with MS course, being lower during relapses and higher in the secondary progressive phase. Further studies are needed to elucidate the potential use of DBP as a biological marker of MS course, but may be of use given the current lack of diagnostic tools for the prediction of MS development and progression.

Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to diverse disorders, remain poorly understood. We determined VDR binding throughout the human genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After calcitriol stimulation, we identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D. VDR binding sites were significantly enriched near autoimmune and cancer associated genes identified from genome-wide association (GWA) studies. Notable genes with VDR binding included IRF8, associated with MS, and PTPN2 associated with Crohn's disease and T1D. Furthermore, a number of single nucleotide polymorphism associations from GWA were located directly within VDR binding intervals, for example, rs13385731 associated with SLE and rs947474 associated with T1D. We also observed significant enrichment of VDR intervals within regions of positive selection among individuals of Asian and European descent. ChIP-seq determination of transcription factor binding, in combination with GWA data, provides a powerful approach to further understanding the molecular bases of complex diseases.

Background: Multiple sclerosis (MS) has a remarkable geographic distribution inversely paralleling that of regional ultraviolet radiation, supporting the hypothesis that vitamin D plays a central role in the disease etiology. The major histocompatibility complex exerts the largest genetic contribution to MS susceptibility, but much risk remains unexplained and direct gene-environment interaction is a strong candidate for this additional risk. Such interactions may hold the key for disease prevention., Recent Developments: Several recent studies strengthen the candidacy of vitamin D as a key player in the causal cascade to MS. This includes a newly identified gene-environment interaction between vitamin D and the main MS-linked HLA-DRB1*1501 allele and evidence showing that vitamin D levels are significantly lower in patients with MS as compared to controls. Also, a recent study in twins with MS supports the notion that vitamin D levels are under regulation by genetic variation in the 1alpha-hydroxylase and vitamin D receptor genes, perhaps pointing to their importance in the disease pathogenesis., Conclusions: These findings have important practical implications for studies of disease mechanisms and prevention. Missing genetic risk may partly be explained by gene-environment interactions. More practically important is that these observations highlight a pressing need to determine if vitamin D supplementation can reduce the risk of multiple sclerosis (MS). However, the timing of action and the tissues in which this interaction takes place are not clear and future studies in prospective cohorts and animal models will be essential for deciphering the role of vitamin D in MS.

Background: Multiple sclerosis (MS) risk is determined by both genes and environment. One of the most striking features of MS is its geographic distribution, particularly the pattern of high MS frequency in areas with low sunlight exposure, the main inducer of vitamin D synthesis. Recent epidemiologic, experimental, and clinical evidence support an effect for low environmental supplies of vitamin D in mediating an increased susceptibility to MS., Objectives: We 1) examined the association of serum 25-hydroxy-vitaminD [25(OH)D] concentrations and MS status and 2) assessed the genetic contribution to serum 25(OH)D concentrations and tested for its association with genetic variants in 2 candidate genes [vitamin D receptor and 1-alpha-hydroxylase (CYP27B1)]., Design: We used a twin study approach, comprising adult pairs identified from the longitudinal population-based Canadian Collaborative Project on Genetic Susceptibility to MS. Monozygotic (MZ; n = 40) and dizygotic (DZ; n = 59) pairs, both concordant and discordant for MS, were studied. End-of-winter serum 25(OH)D concentrations were measured by radioimmunoassay, and genotypes were assessed by single nucleotide polymorphism (SNP) assay., Results: Serum concentrations of 25(OH)D were highly correlated in MS-concordant pairs (r = 0.83, P < 0.001), but they were not significantly associated with having the disease (P = 0.4) when analyzed by logistic regression. Intraclass correlation for 25(OH)D concentration was significantly greater in MZ pairs (MZ, r: 0.71 > DZ r: 0.32, P = 0.006). Significant associations of 2 CYP27B1 SNP variants and 25(OH)D concentrations were observed., Conclusion: The findings indicate important genetic influences on regulation of seasonal circulating 25(OH)D concentrations in MS twins.

Background: Multiple sclerosis (MS) is an inflammatory disease while there are controversies regarding the role of vitamin D supplements in controlling relapse and disability improvement during treatment. Objective: The goal of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplements on MS-related relapse and the Expanded Disability Status Scale (EDSS). Methods: We searched databases to include randomized clinical trials (RCTs) which were published up to October 2018. We included RCTs, being single-blinded or double-blinded or open-label trials in which one of the main outcomes was EDSS and/or relapse after vitamin D supplementation. All statistical analyses were performed using RevMan 5.3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for relapse between treatment arms. The mean difference was calculated for EDSS comparisons. Results: Nine articles were included for analysis. Of these nine studies, five compared vitamin D supplement groups with placebo (group 1 studies), and four compared high- and low-dose vitamin D groups. A total of 561 patients were analyzed. Being treated with vitamin D instead of placebo showed no effect on relapse rate (OR = 0.66, 95% CI = 0.28-1.54) as well as EDSS (mean difference = 0.06, 95%CI [-0.31, 0.42]). The results of studies comparing high- vs. low-dose vitamin D interventions showed no significant effect on relapse rate (OR = 1.08, 95%CI [0.29-4.08] as well as final EDSS (mean difference = 0.17, 95% CI = -0.73, 1.07). Conclusions: Our findings show that vitamin D supplements (high or low dose) have no significant effect on relapse rate and disability during treatment in MS patients. [ABSTRACT FROM AUTHOR]

Background: Epstein–Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). Objectives: To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. Methods: This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo (n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored. Results: The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group (526 (368–1683) to 455 (380–1148) U/mL) compared to the placebo group (432 (351–1280) to 429 (297–1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures. Conclusion: High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism. [ABSTRACT FROM AUTHOR]

Observational studies have shown an association between lower vitamin D levels and higher risk of relapse among people with multiple sclerosis (MS). This has raised interest in potential clinical benefits of vitamin D supplementation in the management of MS. The objectives were to examine the effect of vitamin D based interventions on the relative risk of relapse in MS. Any randomised controlled trial assessing the effect on the relative risk of relapse of any formulation or dose of vitamin D, in participants with MS, was eligible. The inverse variance with random effects model in Review Manager 5.1 was used to calculate the odds ratio of relapses in high dose vitamin D treated patients vs. controls. Five studies were published as of September 2012, yielding a total of 129 high-dose vitamin D-treated patients and 125 controls. We found no significant association between high-dose vitamin D treatment and risk of MS relapse (OR 0.98, 95% CI 0.45–2.16). In conclusion, although no significant association between high-dose vitamin D treatment and risk of MS relapses was found, the studies were limited by several methodological limitations. Further larger, more prolonged studies are merited. [ABSTRACT FROM PUBLISHER]

The article discusses a study regarding the link between Vitamin D and multiple sceloris (MS). Serum 25-hydroxyvitamin (OH) D levels, body mass index (BMI), and amout of sun exposure were measured among 108 matched controls and 110 MS patients in India. HLA-DR typing was conducted using polymerase chain reaction (PCR). Results show an inverse relationship between serum 25(OH) D and MS.

Background Month of birth has previously been described as a risk factor for multiple sclerosis (MS). This has been hypothesised to be related to maternal vitamin D levels during pregnancy, although conclusive evidence to support this is lacking. To date, no large studies of latitudinal variation in the month of birth effect have been performed to advance this hypothesis. Methods Previously published data on month of birth from 151 978 MS patients were compared to expected birth rates. A linear regression model was used to assess the relationship between latitude and observed: expected birth ratio of MS patients for each month. Results Analysis of all reported data demonstrated a significant excess of MS risk in those born in April (observed:expected 1.05, p=0.05) and reduction in risk in those born in October (0.95, p=0.04) and November (0.92 p=0.01). A conservative analysis of 78 488 patients revealed an excess MS risk in those born in April (1.07, p=0.002) and May (1.11, p=0.0006), and a reduced risk in those born in October (ratio 0.94, p=0.004) and November (0.88, p=0.0002). A significant relationship between latitude and observed:expected ratio was demonstrated in December, and borderline significant relationships in May and August. Conclusions Month of birth has a significant effect on subsequent MS risk. This is likely to be due to ultraviolet light exposure and maternal vitamin D levels, as demonstrated by the relationship between risk and latitude. [ABSTRACT FROM AUTHOR]

Several lines of evidence support a role for Epstein–Barr virus (EBV) in the aetiology of multiple sclerosis (MS). This includes the observation that nearly all MS patients show serological markers of past EBV infection. Given the well-known association between MS prevalence and latitude, we investigated whether EBV seropositivity also increases with distance from the equator. We found that the proportion of EBV positive individuals is positively associated with latitude independently of MS status (odds ratio = 1.06, 95% CI = 1.02–1.09, p = 0.002). Latitude-related factors may be implicated in the immune response to EBV and its role in MS aetiology. [ABSTRACT FROM AUTHOR]

People with multiple sclerosis (MS) have many reasons to have low bone mineral density and an increased fracture risk. Osteoporosis is a major cause of morbidity and mortality, and is more common in people with MS than the general population. A number of studies have examined the relationship between multiple sclerosis and reduced bone mineral density. In this topical review we seek to address the risk of low bone mineral density, osteoporosis and fractures associated with MS, and make practical suggestions as to how this pertinent issue may be approached in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Genome-wide association studies (GWAS) have been conducted on many complex diseases with the aim of identifying common genetic variants important in disease susceptibility. It is rare for these to consider environmental factors when calculating the odds ratios for variants associated with disease. We modelled the effect of an environmentally-dependent genetic risk locus and showed that, despite a relatively low overall odds ratio, environmental exposure was able to conceal a large true effect size on disease susceptibility in exposed individuals. This model was applied to vitamin D deficiency in multiple sclerosis and raised the possibility of large magnitudes of concealed effect in loci responsive to vitamin D in this disease. In the post-GWAS era, efforts should be made to elucidate potential gene–environment interactions involved in complex traits in order for true effects on disease risk to be realised. [Copyright &y& Elsevier]

Multiple sclerosis (MS) is a complex trait in which allelic variation in the MHC class II region exerts the single strongest effect on genetic risk. Epidemiological data in MS provide strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of this disease. Growing evidence implicates sunlight or vitamin D as a key environmental factor in aetiology. We hypothesised that this environmental candidate might interact with inherited factors and sought responsive regulatory elements in the MHC class II region. Sequence analysis localised a single MHC vitamin D response element (VDRE) to the promoter region of HLA-DRB1. Sequencing of this promoter in greater than 1,000 chromosomes from HLA-DRB1 homozygotes showed absolute conservation of this putative VDRE on HLA-DRB1*15 haplotypes. In contrast, there was striking variation among non-MS-associated haplotypes. Electrophoretic mobility shift assays showed specific recruitment of vitamin D receptor to the VDRE in the HLA-DRB1*15 promoter, confirmed by chromatin immunoprecipitation experiments using lymphoblastoid cells homozygous for HLA-DRB1*15. Transient transfection using a luciferase reporter assay showed a functional role for this VDRE. B cells transiently transfected with the HLA-DRB1*15 gene promoter showed increased expression on stimulation with 1,25-dihydroxyvitamin D3 (P = 0.002) that was lost both on deletion of the VDRE or with the homologous "VDRE" sequence found in non-MS-associated HLA-DRB1 haplotypes. Flow cytometric analysis showed a specific increase in the cell surface expression of HLA-DRB1 upon addition of vitamin D only in HLA-DRB1*15 bearing lymphoblastoid cells. This study further implicates vitamin D as a strong environmental candidate in MS by demonstrating direct functional interaction with the major locus determining genetic susceptibility. These findings support a connection between the main epidemiological and genetic features of this disease with major practical implications for studies of disease mechanism and prevention. [ABSTRACT FROM AUTHOR]

The authors reflect on the study concerning the interaction between Vitamin D and multiple sclerosis (MS). The authors relate the article "Multiple Sclerosis Journal," by Cox and colleagues which highlights a single nucleotide polymorphism (SNP) in VDR associated with MS susceptibility. They add that the link between a SNP associated with MS susceptibility is important, since it suggests that at least some of the genetic predisposition to MS may be modifiable.

Background and purpose: Previous studies have described a seasonal pattern of MS relapse risk. Vitamin D and infectious triggers are two major candidate environmental risk factors proposed to account for this effect. We aimed to assess MS admissions in Scotland for a possible effect of seasonality. Methods: Acute admissions with MS were obtained from the Scottish Morbidity Register between 1997 and 2009. We compared the pattern of these to admissions with other diagnoses. Results: We obtained data on 7098 MS and 6 243 690 non-MS acute and day-case admissions. We found a significant difference in acute MS admissions compared with admissions with other diagnoses (P = 0.0015). There was a significant excess of Scottish MS admissions in April and June with nadirs in March and October. Conclusions: Admissions with MS show a significant seasonal variation throughout the year. Further work will be needed to identify candidate environmental factors with certainty. [ABSTRACT FROM AUTHOR]

Abstract: Autoimmune mechanisms are thought to have a major role in the pathogenesis of multiple sclerosis (MS) and vitamin D is hypothesised to contribute to disease susceptibility. Cow''s milk allergy (CMA) is a common childhood allergy arising from an immune system imbalance and can also lead to vitamin D deficiency due to dairy food avoidance. Here, we investigated whether or not CMA influences the subsequent risk to develop MS in a population-based cohort. We identified 6638 MS index cases and 2509 spousal controls with CMA information from the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). Frequency of CMA was compared between index cases and controls. No significant differences were found. Childhood CMA thus does not appear to be a risk factor for MS. [Copyright &y& Elsevier]

Background: Multiple sclerosis (MS) is an inflammatory disease, which has a wide range of effects on patients. There are controversies regarding the role of vitamin D in clinical and laboratory improvements in MS patients. Objective: The aim of this systematic review protocol is to evaluate the efficacy of vitamin D supplements on relapse rate, gadolinium-enhancing lesions of magnetic resonance imaging (MRI), and cytokine profiles. Methods: We will search PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, ProQuest, American College of Physicians Journal Club database, Health Technology Assessment Database (The Cochrane Collaboration), and National Health System Economic Evaluation Database (The Cochrane Collaboration) and gray literature including reference of included studies and conference abstracts. Clinical trials reporting the effect of any doses of vitamin D on relapse rate, gadolinium-enhancing lesions of MRI, and cytokine profiles will be included. In total, 2 independent researchers will independently assess the studies, extract data, and evaluate the quality of primary studies. Results: This systematic review was started in September 2017 and the process is continuing. The included articles are evaluated and researchers are going to extract the data. Conclusions: To our knowledge, this will be the first comprehensive systematic review aiming to assess the effect of vitamin D supplements on clinical and para-clinical outcomes in patients with multiple sclerosis. International Registered Report Identifier (IRRID): DERR1-10.2196/12045 We help JMIR researchers to raise funds to pursue their research and development aimed at tackling important health and technology challenges. If you would like to show your support for this author, please donate using the button below. The funds raised will directly benefit the corresponding author of this article (minus 8% admin fees). Your donations will help this author to continue publishing open access papers in JMIR journals. Donations of over $100 may also be acknowledged in future publications. Suggested contribution levels: $20/$50/$100 [ABSTRACT FROM AUTHOR]

The authors discuss hypovitaminosis D as one of the most promising candidates in terms of clinical implications and prospects for the prevention of multiple sclerosis (MS). They mention the proposal of a protective effect for vitamin D supplementation following observations showing the prevalence of MS that is inversely related to sunlight exposure. They also cite the origin of increased female preponderance of MS over the past years.

An introduction to the journal is presented in which the editor discusses various reports within the issue on topics related to the immunology of multiple sclerosis (MS) including the role of vitamin D deficiency on MS, mitochondria on central nervous system (CNS) damage, and heterogeneity of MS.