Risk Factor For Multiple Sclerosis Research Articles

Waterpipe smoking associated with multiple sclerosis: A population-based incident case–control study

Background: While cigarette and passive smoking have been identified as modifiable risk factors for multiple sclerosis (MS), there is no report regarding Waterpipe smoking–MS association. Objective: We examined the association of Waterpipe, tobacco, and passive smoking with MS. Methods: Population-based incident case–control study in Iran with 547 incident cases and 1057 general population controls (7 August 2013–17 February 2015). Logistic regression model was used. Multiplicative along with additive interaction was assessed using product term and Synergy Index (SI), respectively, and the population attributable fractions (PAFs) were calculated. Results: Having ever smoked Waterpipe, tobacco, or being exposed to passive smoking were all significantly associated with MS (odds ratio (OR) = 1.77 (1.36–2.31), OR = 1.69 (1.24–2.31), and OR = 1.85 (1.48–2.32), respectively). Clear dose–response associations were observed with the duration exposed (p < 0.001 for all three) and the amount smoked (p < 0.001 for Waterpipe and tobacco). Those who had all three types of smoking had an odds that was 4.1 times higher than those without any type. The three types of smoking jointly contributed to 30.9% of the MS incidence. Conclusion: We identified Waterpipe smoking as a novel risk factor for MS. Given the global increase in Waterpipe smoking, especially among young adults, this finding reinforces the need for public health interventional and educational programs to combat this global increase.

RETRACTED ARTICLE: Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis

Statement of Retraction We, the Editors and Publisher of the journal Immunological Investigations, have retracted the following article: Merhdad Farrokhi, Pedram Moeini, Mohammada Fazilati, Habibollah Nazem, Shahla Faraji, Zahra Saadatpour, Elyas Fadaei, Leila Saadatpour, Ali Rezaei, Sadra Ansaripour and Ali Amani-Beni (2016) Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis, Immunological Investigations, DOI: https://doi.org/10.1080/08820139.2016.1226897 Since publication, significant concerns have been raised about the author affiliations, ethical approval, and the integrity of the data in the article. When approached for an explanation, the authors provided responses to our queries regarding the flow cytometry data, but they have not sufficiently addressed all of our concerns. In particular, the authors and institution did not respond to our requests for proof that the research was conducted at the Isfahan University of Medical Sciences or provide proof of ethical approval. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our Editorial Policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Feasibility study for remote assessment of cognitive function in multiple sclerosis.

Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (p<0.001). Cases who did complete testing did not differ in terms of perceived cognitive deficit compared to cases that did participate. More severe disease, smoking, and being male were associated with a lower TICS-M score among cases (p<0.001). The TICS-M score was significantly lower in cases compared to controls (p=0.007). Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.

Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population-Based Cross-Sectional Study in South-Western Sardinia.

BackgroundSouth-Western Sardinia (SWS) is a high risk area for Multiple Sclerosis (MS) with high prevalence and spatial clustering; its population is genetically representative of Sardinians and presents a peculiar environment. We evaluated the MS environmental risk of specific heavy metals (HM) and geographical factors such as solar UV exposure and urbanization by undertaking a population-based cross-sectional study in SWS.MethodsGeochemical data on HM, UV exposure, urbanization and epidemiological MS data were available for all SWS municipalities. Principal Component Analysis (PCA) was applied to the geochemical data to reduce multicollinearity and confounding criticalities. Generalized Linear Mixed Models (GLMM) were applied to evaluate the causal effects of the potential risk factors, and a model selection was performed using Akaike Information Criterion.ResultsThe PCA revealed that copper (Cu) does not cluster, while two component scores were extracted: 'basic rocks', including cobalt, chromium and nickel, and 'ore deposits', including lead and zinc. The selected multivariable GLMM highlighted Cu and sex as MS risk factors, adjusting for age and 'ore deposits'. When the Cu concentration increases by 50 ppm, the MS odds are 2.827 (95% CI: 1.645; 5.07) times higher; females have a MS odds 2.04 times (95% CI: 1.59; 2.60) higher than males.ConclusionsThe high frequency of MS in industrialized countries, where pollution by HM and CO poisoning is widespread, suggests a relationship between environmental exposure to metals and MS. Hence, we suggested a role of Cu homeostasis in MS. This is a preliminary study aimed at generating hypotheses that will need to be confirmed further.

Persian adaptation of a questionnaire of environmental risk factors in multiple sclerosis (EnvIMS-Q)

BackgroundIt seems that gene-environment interaction play most important role in Multiple Sclerosis development. Increasing the incidence and prevalence of MS during the recent decades in the low prevalence area such as Iran is explained better by environment factors. Environmental Risk Factors in Multiple Sclerosis (the ‘EnvIMS-Q′) is a 6-page self-administered questionnaire for case control studies. Objectivesthe objectives of study are validation and adaptation of the EnvIMS-Q′ then development of a Persian version for case control studies in Persian population. MethodsThis questionnaire translated literally and in culturally relevant form, then content validation process was done by three groups’ experts. According to giving rating to each item, each section and the whole instrument, we calculated their content validation indexes and also added some new questions and a new section to EnvIMS-Q. Finally, we analyzed repeatability of the answers within a 4 weeks interval. ResultsRelevancy and clarity indexes of all items were more than 80%. Scale relevancy index equaled 99% and scale clarity index equaled 97%. Repeatability of most items was acceptable. Conclusionsthe use of standardized validated questionnaires will assist the researchers to perform local studies on the role of environmental factors on the basis of reliable data.

Environmental and genetic factors in pediatric inflammatory demyelinating diseases.

The onset of multiple sclerosis (MS) occurs in childhood in about 5% of all patients with MS. The disease in adults has a complex genetic and environmental inheritability. One of the main risk factors, also confirmed in pediatric MS, is HLA DRB1*1501 In addition to genetic factors, a large part of disease susceptibility in adults is conferred by environmental risk factors such as low vitamin D status, exposure to cigarette smoking, and remote Epstein-Barr virus (EBV) infection. In children, both exposure to cigarette smoking and prior EBV infection have been reported consistently as risk factors for MS. The role of vitamin D remains to be confirmed in this age category. Finally, although very likely critical in disease processes, few gene-environment interactions and epigenetic changes have been reported for adult and pediatric MS susceptibility. Of interest, some of the risk factors for MS have also been associated with disease course modification, such as low 25(OH) vitamin D serum levels in pediatric and adult MS. Age is also a clear disease modifier of clinical, CSF, and MRI phenotype in children with the disease. Finally, although much has yet to be unraveled regarding molecular processes at play in MS, there is a larger gap in our knowledge of genetic and environmental risk factors for pediatric neuromyelitis optica spectrum disorders and acute disseminated encephalomyelitis and only collaborative studies will answer those questions.

Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein.

EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV-infected B cells and CD20(+) spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40-48 core epitope. Finally, LCV infection also induced expression of LC3-II(+) cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40-48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40-48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs.

Risk factors in multiple sclerosis: a population-based case-control study in Sicily. Background and methods.

Incidence of multiple sclerosis (MS) has steeply increased over time during the last 30years in the city of Catania. We carried out a population-based case-control study to evaluate the possible role of both environmental and genetic factors. From 1975 to 2004 in Catania, 367 MS patients diagnosed according to the Poser's criteria had the onset of disease. A sample of MS patients was randomly selected from this incident cohort. Three controls matched by age and sex were randomly selected from the rosters of 14GPs. Controls were proportionally selected according to the distribution by municipality of the target population using a multistage sampling methods. All cases and controls underwent a face-to-face interview to record information concerning environmental factors and a blood sample was taken for serological and genetic analysis. 164 MS patients (64% women; mean age of 46.4±10.7) and 481 controls (69% women; mean age of 47.7±14.8) were enrolled in the study. The distribution of the whole population and the selected controls by municipalities was similar. A blood sample was taken from 150 MS cases and from 337 controls. At the end of the enrolment, we obtained a representative sample of the MS cases and population controls avoiding possible selection bias. Participation rate was very high also concerning the collection of biological specimens.

Time- and Region-Specific Season of Birth Effects in Multiple Sclerosis in the United Kingdom.

The reports of seasonal variation in the births of people who later develop multiple sclerosis (MS) have been challenged and attributed to the background pattern in the general population, resulting in a false association. To study the seasonality of MS births after adjusting for temporal and regional confounding factors. A study was conducted using case-control data from 8 MS-specialized centers from the United Kingdom, MS cases from a population-based study in the Lothian and Border regions of Scotland, and death records from the UK Registrar General. Participants included 21 138 patients with MS and control data from the UK Office of National Statistics and the UK government office regions. The seasonality of MS births was evaluated using the Walter and Elwood test, after adjusting for temporal and regional variations in the live births of the UK population. The study was conducted from January 16, 2014, to September 2, 2015. Diagnosis of multiple sclerosis. Analysis of the general population indicated that seasonal differences are present across time and region in the United Kingdom, with both factors contributing to the monthly distribution of live births. We were able to demonstrate that, when adjusting for the temporal and regional variations in the live births of the UK population, there was a significant season of birth effect in patients with MS, with an increased risk of disease in the peak month (April) compared with the trough month (November) (odds ratio, 1.24; 95% CI, 1.10-1.41) and 15.68% fewer people who developed MS being born in November (observed to expected birth ratio, 0.840; 95% CI, 0.76-0.92). Season of birth is a risk factor for MS in the United Kingdom and cannot be attributed to the background pattern in the general population. The reasons for the variations in birth rates in the general population are unclear, but not taking them into consideration could lead to false-positive associations.

Epidemiology of Major Neurodegenerative Diseases in Women: Contribution of the Nurses' Health Study.

To review the contribution of the Nurses' Health Study (NHS) to identifying the role of lifestyle, diet, and genetic or biological factors in several neurodegenerative diseases, including cognitive decline, multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. We completed a narrative review of the publications of the NHS and NHS II between 1976 and 2016. In primary findings for cognitive function, higher intake of nuts, moderate alcohol consumption, and higher physical activity levels were associated with better cognitive function. Flavonoids, physical activity, and postmenopausal hormone therapy were related to cognitive decline over 2 to 6 years. The NHS also has been integral in establishing Epstein-Barr virus infection, inadequate vitamin D nutrition, cigarette smoking, and obesity as risk factors for multiple sclerosis and inverse associations between cigarette smoking and caffeine and risk of Parkinson's disease. Increased risk of amyotrophic lateral sclerosis has been associated with cigarette smoking and decreased risk associated with obesity. The NHS has provided invaluable resources on neurodegenerative diseases and contributed to their etiological understanding. We anticipate that the NHS cohorts will continue to make important contributions to the field of neurodegenerative diseases.

Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors

Background: Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood. Objective: We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors. Methods: Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level. Results and conclusion: Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR < 0.01, of which 65 are novel. These pleiotropic loci were located on 21 different chromosomes. Our findings point to overlapping pathobiology between clinically diagnosed MS and cardiovascular risk factors and identify novel common variants associated with increased MS risk.

Dietary Inflammatory Index and Risk of Multiple Sclerosis in a Case-Control Study from Iran

Background: Diet and inflammation have been suggested to be important risk factors for multiple sclerosis (MS). Objectives: In this study, we examined the ability of the dietary inflammatory index (DII) to predict MS in a case-control study conducted in Iran. Methods: This study included 68 MS cases and 140 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Logistic regression models were used to estimate ORs adjusted for age, energy, sex, body mass index, season of birth, rubella history, history of routine exercise before MS, smoking and history of consumption of cow's milk in the first 2 years of life. Results: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of MS, with the DII being used both as a continuous variable (OR_continuous 1.66; 95% CI 1.19-2.31; 1 unit increase corresponding to ≈15% of its range in the current study) and a categorical variable (OR_{DII (>1.43 vs.}_≤_1.43) 2.68; 95% CI 1.15-6.26). Conclusions: These results indicate that a pro-inflammatory diet is associated with increased risk of MS.

Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing.

Multiple sclerosis (MS) is a debilitating immune-mediated neurological disorder affecting young adults. MS is primarily relapsing-remitting, but neurodegeneration and disability accumulate from disease onset. The most commonly used mouse MS models exhibit a monophasic immune response with fast accumulation of neurological damage that does not allow the study of progressive neurodegeneration. The chronic relapsing and secondary progressive EAE (pEAE) Biozzi ABH mouse model of MS exhibits a reproducible relapsing-remitting disease course that slowly accumulates permanent neurological deficit and develops a post-relapsing progressive disease that permits the study of demyelination and neurodegeneration. RNA sequencing (RNAseq) was used to explore global gene expression in the pEAE Biozzi ABH mouse. Spinal cord tissue RNA from pEAE Biozzi ABH mice and healthy age-matched controls was sequenced. 2,072 genes were differentially expressed (q<0.05) from which 1,397 were significantly upregulated and 675 were significantly downregulated. This hypothesis-free investigation characterised the genomic changes that describe the pEAE mouse model. The differentially expressed genes revealed a persistent immunoreactant phenotype, combined with downregulation of the cholesterol biosynthesis superpathway and the LXR/RXR activation pathway. Genes differentially expressed include the myelination genes Slc17a7, Ugt8A and Opalin, the neuroprotective genes Sprr1A, Osm and Wisp2, as well as genes identified as MS risk factors, including RGs14 and Scap2. Novel genes with unestablished roles in EAE or MS were also identified. The identification of differentially expressed novel genes and genes involved in MS pathology, opens the door to their functional study in the pEAE mouse model which recapitulates some of the important clinical features of progressive MS.

Shift work at young age is associated with increased risk of multiple sclerosis in a Danish population

BackgroundEpidemiological studies suggest an important role for environmental factors in developing multiple sclerosis (MS). Furthermore several studies have indicated that the effect of environmental factors may be especially pronounced in adolescents. Recently only one study investigated and found that shift work at young age is associated with an increased risk of developing MS. In this study we focused on the effect of shift work in the vulnerable period between 15–19 years. ObjectiveThe aim of this study was to investigate the association between shift work at young age and the risk of developing MS. MethodsWe performed a large case-control study including 1723 patients diagnosed with MS and 4067 controls. MS patients were recruited from the Danish Multiple Sclerosis Biobank and controls from The Danish Blood Donor Study. Information on working patterns and lifestyle factors was obtained using a comprehensive lifestyle-environmental factor questionnaire with participants enrolled between 2009 and 2014. Logistic regression models were used to investigate the association between shift work at age 15–19 years and the subsequent risk of MS and were controlled for effects due to established MS risk factors. ResultsWe found a statistically significant association when total numbers of night shifts were compared with non-shift workers. For every additional 100 night shifts the odds ratio (OR) for MS was 1.20 (95% confidence interval (CI), 1.08–1.34, p=0.001). Increasing intensity of shift work also increased MS risk. For every additional night per month the OR was 1.04 (95% CI, 1.01–1.06, p=0.002). Duration of shift work in years was not associated with risk of MS. ConclusionThis study supports a statistically significant association between shift work at age 15–19 years and MS risk.

T-cell activation and HLA-regulated response to smoking in the deep airways of patients with multiple sclerosis

Cigarette smoking is a risk factor for multiple sclerosis (MS), and the risk is further multiplied for HLA-DRB1*15+ smokers. To define the smoke-induced immune responses in the lung we performed bronchoscopy with bronchoalveolar lavage (BAL) on smokers and non-smokers, both MS-patients and healthy volunteers. In the BAL, non-smokers with MS showed an increased preformed CD40L expression in CD4+ T-cells while smokers displayed an increase in proliferating (Ki-67+) T-cells. In addition, our results confirm that smoking induces an increase of alveolar macrophages in BAL, and further defined a significant attenuation of this response in carriers of the HLA-DRB1*15 allele, in both MS patients and healthy controls. This first systematic investigation of the immune response in the lungs of smokers and non-smokers diagnosed with MS, thus suggests an MS-associated lung T-cell phenotype, involvement of a specific T-cell response to smoke, and a genetic regulation of the macrophage response.

Novel Insights into the Multiple Sclerosis Risk Gene ANKRD55.

An intronic variant in ANKRD55, rs6859219, is a genetic risk factor for multiple sclerosis, but the biological reasons underlying this association are unknown. We characterized the expression of ANKRD55 in human PBMCs and cell lines. Three ANKRD55 transcript variants (Ensembl isoforms 001, 005, and 007) could be detected in PBMCs and CD4(+) T cells but were virtually absent in CD8(+), CD14(+), CD19(+), and CD56(+) cells. Rs6859219 was significantly associated with ANKRD55 transcript levels in PBMCs and CD4(+) T cells and, thus, coincides with a cis-expression quantitative trait locus. The processed noncoding transcript 007 was the most highly expressed variant in CD4(+) T cells, followed by 001 and 005, respectively, but it was not detected in Jurkat, U937, and SH-SY5Y cell lines. Homozygotes for the risk allele produced more than four times more transcript copies than did those for the protective allele. ANKRD55 protein isoforms 005 and 001 were predominantly located in the nucleus of CD4(+) T cells and Jurkat and U937 cells. ANKRD55 was produced by primary cultures of murine hippocampal neurons and microglia, as well as by the murine microglial cell line BV2, and it was induced by inflammatory stimuli. ANKRD55 protein was increased in the murine mouse model of experimental autoimmune encephalomyelitis. Flow cytometric analysis of CNS-infiltrating mononuclear cells showed that CD4(+) T cells and monocytes expressed ANKRD55 in experimental autoimmune encephalomyelitis mice, with the higher fluorescence intensity found in CD4(+) cells. A low percentage of microglia also expressed ANKRD55. Together, these data support an important role for ANKRD55 in multiple sclerosis and neuroinflammation.

Longitudinal BMI trajectories in multiple sclerosis: Sex differences in association with disease severity

BackgroundAdolescent obesity is a risk factor for multiple sclerosis (MS), but little is known about changes in body mass index (BMI) after MS onset. ObjectiveTo assess the relationship between MS and longitudinal changes in BMI. MethodsWe analyzed prospectively collected BMIs in a cohort of patients with adult-onset MS and matched adult healthy controls (HC) gathered from the same hospital network central clinical data registry. ResultsWe made three main observations. First, at baseline MS patients had a significantly higher BMI than HC (age- and sex- adjusted mean difference=0.57; 95% CI: 0.15, 0.99; p=0.008). Second, a significant age by MS status interaction was observed (p<0.0001), such that in MS, BMIs did not increase significantly higher in older individuals, whereas BMIs in HCs were higher with increasing age. Third, we observed sex-specific associations with disease severity: higher BMI was associated with higher cross-sectional EDSS in women, but with lower EDSS in men (p=0.003, N=758). There were no longitudinal associations between BMI and EDSS in either sex or in the entire cohort (p=0.65, N=772). ConclusionAfter MS onset, patients may not experience age-expected increases in BMI. BMI may have sex-specific associations with MS disability scores. More refined measures of body composition are warranted in future studies to distinguish adiposity from muscle mass.

IL-7 receptor polymorphisms is related to signaling strength which is associated with autoimmune T cells activation in multiple sclerosis

Abstract IL-7 is required for survival of most T cell subsets and generally promotes T cell immune responses. Loss of functions of IL-7R in human has been known to cause severe combined immunodeficiency. Somatic gain of function mutations of IL-7R have been found in childhood T-cell acute lymphoblastic leukemia (T-ALL), these mutations usually occur in region of residue 244 in the exon 6 and lead to insertion of multiple amino acids. More recently, polymorphisms in IL-7R have been shown be a risk factor for multiple sclerosis (MS) and some autoimmune diseases. The polymorphysims that affects risk to most of these immunopathologies is T244/I, the same region harboring gain-of-function mutations in T-ALL. To investigate the mechanism of IL-7R variants association with MS and seek new therapeutic approaches directed to IL-7R pathway, we hypothesize that the functional significance of the T244/I polymorphism in IL-7R is related to increased signaling. To test our hypothesis, the T244 and I244 alleles of IL7R are transfected into BaF3 cells. The high risk allele T244 induces stronger Stat5 activation and promotes better survival of BaF3 cells. We further examine the strength of signaling in vivo in mice. IL-7R deficient bone marrow hematopoietic progenitors are transduced by retroviral infection with T244 or I244 allele and transferred to Rag1 deficient mice. Human IL-7R rescues T cell development in mice. Consistent with the in vitro study, the CD8 cells harboring the high risk allele T244 display stronger Stat5 activation compared with cells with I244. Our preliminary study suggests that high risk allele T244 of IL-7R signals stronger than allele I244, and this may promote activation of autoimmune T calls in MS and other autoimmune diseases.

Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort.

Vitamin D has been associated with a decreased risk of multiple sclerosis (MS) in adulthood; however, some, but not all, previous studies have suggested that in utero vitamin D exposure may be a risk factor for MS later in life. To examine whether serum 25-hydroxyvitamin D (25[OH]D) levels in early pregnancy are associated with risk of MS in offspring. Prospective, nested case-control study in the Finnish Maternity Cohort conducted in May 2011. We identified 193 individuals with a diagnosis of MS before December 31, 2009, whose mothers are in the Finnish Maternity Cohort and had an available serum sample from the pregnancy with the affected child. We matched 176 cases with 326 controls on region of birth in Finland, date of maternal serum sample collection, date of mother's birth, and date of child's birth. Maternal serum 25(OH)D levels were measured using a chemiluminescence assay. The risk of MS among offspring and association with maternal 25(OH)D levels were the main outcomes. Conditional logistic regression was used and further adjusted for sex of the child, gestational age at the time of sample collection, and season of sample collection to estimate the relative risks and 95% CIs. Of the 193 cases in the study, 163 were female. Of the 331 controls in the study, 218 were female. Seventy percent of serum samples were collected during the first trimester of pregnancy. The mean (SD) maternal vitamin D levels were in the insufficient vitamin D range, but higher in maternal control than case samples (15.02 [6.41] ng/mL vs 13.86 [5.49] ng/mL [to convert to nanomoles per liter, multiply by 2.496]). Maternal vitamin D deficiency (25[OH]D levels <12.02 ng/mL) during early pregnancy was associated with a nearly 2-fold increased risk of MS in the offspring (relative risk, 1.90; 95% CI, 1.20-3.01; P = .006) compared with women who did not have deficient 25(OH)D levels. There was no statistically significant association between the risk of MS and increasing serum 25(OH)D levels (P = .12). Insufficient maternal 25(OH)D during pregnancy may increase the risk of MS in offspring.

The possible effects of the solar and geomagnetic activity on multiple sclerosis

ObjectivesIncreasing observational evidence on the biological effects of Space Weather suggests that geomagnetic disturbances may be an environmental risk factor for multiple sclerosis (MS) relapses. In the present study, we aim to investigate the possible effect of geomagnetic disturbances on MS activity. Patients and methodsMS patient admittance rates were correlated with the solar and geophysical data covering an eleven-year period (1996–2006, 23rd solar cycle). We also examined the relationship of patterns of the solar flares, the coronal mass ejections (CMEs) and the solar wind with the recorded MS admission numbers. ResultsThe rate of MS patient admittance due to acute relapses was found to be associated with the solar and geomagnetic events. There was a “primary” peak in MS admittance rates shortly after intense geomagnetic storms followed by a “secondary” peak 7–8 months later. ConclusionWe conclude that the geomagnetic and solar activity may represent an environmental health risk factor for multiple sclerosis and we discuss the possible mechanisms underlying this association. More data from larger case series are needed to confirm these preliminary results and to explore the possible influence of Space Weather on the biological and radiological markers of the disease.